RBCC

Full text data of HIST1H3A

HIST1H3A (H3FJ) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Histone H3.1 (Histone H3/a; Histone H3/b; Histone H3/c; Histone H3/d; Histone H3/f; Histone H3/h; Histone H3/i; Histone H3/j; Histone H3/k; Histone H3/l)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P68431
ID H31_HUMAN Reviewed; 136 AA.
AC P68431; A0PJT7; A5PLR1; P02295; P02296; P16106; Q6ISV8; Q6NWP8;
read moreAC Q6NWP9; Q6NXU4; Q71DJ3; Q93081;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 112.
DE RecName: Full=Histone H3.1;
DE AltName: Full=Histone H3/a;
DE AltName: Full=Histone H3/b;
DE AltName: Full=Histone H3/c;
DE AltName: Full=Histone H3/d;
DE AltName: Full=Histone H3/f;
DE AltName: Full=Histone H3/h;
DE AltName: Full=Histone H3/i;
DE AltName: Full=Histone H3/j;
DE AltName: Full=Histone H3/k;
DE AltName: Full=Histone H3/l;
GN Name=HIST1H3A; Synonyms=H3FA;
GN and
GN Name=HIST1H3B; Synonyms=H3FL;
GN and
GN Name=HIST1H3C; Synonyms=H3FC;
GN and
GN Name=HIST1H3D; Synonyms=H3FB;
GN and
GN Name=HIST1H3E; Synonyms=H3FD;
GN and
GN Name=HIST1H3F; Synonyms=H3FI;
GN and
GN Name=HIST1H3G; Synonyms=H3FH;
GN and
GN Name=HIST1H3H; Synonyms=H3FK;
GN and
GN Name=HIST1H3I; Synonyms=H3FF;
GN and
GN Name=HIST1H3J; Synonyms=H3FJ;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H3B).
RX PubMed=6647026; DOI=10.1093/nar/11.21.7409;
RA Zhong R., Roeder R.G., Heintz N.;
RT "The primary structure and expression of four cloned human histone
RT genes.";
RL Nucleic Acids Res. 11:7409-7425(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3013246;
RA Marashi F., Helms S., Shiels A., Silverstein S., Greenspan D.S.,
RA Stein G., Stein J.;
RT "Enhancer-facilitated expression of prokaryotic and eukaryotic genes
RT using human histone gene 5' regulatory sequences.";
RL Biochem. Cell Biol. 64:277-289(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (H3FD).
RX PubMed=1916825; DOI=10.1016/0888-7543(91)90183-F;
RA Albig W., Kardalinou E., Drabent B., Zimmer A., Doenecke D.;
RT "Isolation and characterization of two human H1 histone genes within
RT clusters of core histone genes.";
RL Genomics 10:940-948(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8227173; DOI=10.1002/jcb.240520402;
RA Kardalinou E., Eick S., Albig W., Doenecke D.;
RT "Association of a human H1 histone gene with an H2A pseudogene and
RT genes encoding H2B.1 and H3.1 histones.";
RL J. Cell. Biochem. 52:375-383(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RA Runge D., Eick S., Doenecke D.;
RT "Expression of human histone h1.1 and the nearby core histones.";
RL Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H3I).
RX PubMed=9031620; DOI=10.1016/S0378-1119(96)00582-3;
RA Albig W., Meergans T., Doenecke D.;
RT "Characterization of the H1.5 gene completes the set of human H1
RT subtype genes.";
RL Gene 184:141-148(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H3D; HIST1H3F AND HIST1H3G).
RX PubMed=9119399; DOI=10.1006/geno.1996.4592;
RA Albig W., Kioschis P., Poustka A., Meergans K., Doenecke D.;
RT "Human histone gene organization: nonregular arrangement within a
RT large cluster.";
RL Genomics 40:314-322(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H3H AND HIST1H3J).
RX PubMed=9439656; DOI=10.1007/s004390050630;
RA Albig W., Doenecke D.;
RT "The human histone gene cluster at the D6S105 locus.";
RL Hum. Genet. 101:284-294(1997).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (HIST1H3A; HIST1H3B; HIST1H3C;
RP HIST1H3D; HIST1H3E; HIST1H3F; HIST1H3G; HIST1H3H; HIST1H3I; HIST1H3J).
RX PubMed=12408966; DOI=10.1016/S0888-7543(02)96850-3;
RA Marzluff W.F., Gongidi P., Woods K.R., Jin J., Maltais L.J.;
RT "The human and mouse replication-dependent histone genes.";
RL Genomics 80:487-498(2002).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus, Stomach, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [14]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Spleen;
RX PubMed=7309716;
RA Ohe Y., Iwai K.;
RT "Human spleen histone H3. Isolation and amino acid sequence.";
RL J. Biochem. 90:1205-1211(1981).
RN [15]
RP PROTEIN SEQUENCE OF 2-20, METHYLATION AT LYS-10; LYS-28 AND LYS-37,
RP PHOSPHORYLATION AT THR-4; SER-11 AND SER-29, ACETYLATION AT LYS-10 AND
RP LYS-15, AND MASS SPECTROMETRY.
RX PubMed=16185088; DOI=10.1021/bi050906n;
RA Garcia B.A., Barber C.M., Hake S.B., Ptak C., Turner F.B., Busby S.A.,
RA Shabanowitz J., Moran R.G., Allis C.D., Hunt D.F.;
RT "Modifications of human histone H3 variants during mitosis.";
RL Biochemistry 44:13202-13213(2005).
RN [16]
RP PROTEIN SEQUENCE OF 58-64; 117-120 AND 124-135, AND PHOSPHORYLATION AT
RP SER-11 AND SER-29.
RX PubMed=10464286; DOI=10.1074/jbc.274.36.25543;
RA Goto H., Tomono Y., Ajiro K., Kosako H., Fujita M., Sakurai M.,
RA Okawa K., Iwamatsu A., Okigaki T., Takahashi T., Inagaki M.;
RT "Identification of a novel phosphorylation site on histone H3 coupled
RT with mitotic chromosome condensation.";
RL J. Biol. Chem. 274:25543-25549(1999).
RN [17]
RP METHYLATION AT LYS-10.
RX PubMed=11242053; DOI=10.1038/35065132;
RA Lachner M., O'Carroll D., Rea S., Mechtler K., Jenuwein T.;
RT "Methylation of histone H3 lysine 9 creates a binding site for HP1
RT proteins.";
RL Nature 410:116-120(2001).
RN [18]
RP PHOSPHORYLATION AT SER-11 AND SER-29.
RX PubMed=11856369; DOI=10.1046/j.1356-9597.2001.00498.x;
RA Goto H., Yasui Y., Nigg E.A., Inagaki M.;
RT "Aurora-B phosphorylates Histone H3 at serine28 with regard to the
RT mitotic chromosome condensation.";
RL Genes Cells 7:11-17(2002).
RN [19]
RP PHOSPHORYLATION AT SER-11 AND THR-12.
RX PubMed=12560483; DOI=10.1093/nar/gkg176;
RA Preuss U., Landsberg G., Scheidtmann K.H.;
RT "Novel mitosis-specific phosphorylation of histone H3 at Thr11
RT mediated by Dlk/ZIP kinase.";
RL Nucleic Acids Res. 31:878-885(2003).
RN [20]
RP METHYLATION AT ARG-18.
RX PubMed=15471871; DOI=10.1074/jbc.M410021200;
RA Ananthanarayanan M., Li S., Balasubramaniyan N., Suchy F.J.,
RA Walsh M.J.;
RT "Ligand-dependent activation of the farnesoid X-receptor directs
RT arginine methylation of histone H3 by CARM1.";
RL J. Biol. Chem. 279:54348-54357(2004).
RN [21]
RP METHYLATION AT LYS-80.
RX PubMed=15525939; DOI=10.1038/nature03114;
RA Huyen Y., Zgheib O., Ditullio R.A. Jr., Gorgoulis V.G., Zacharatos P.,
RA Petty T.J., Sheston E.A., Mellert H.S., Stavridi E.S.,
RA Halazonetis T.D.;
RT "Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand
RT breaks.";
RL Nature 432:406-411(2004).
RN [22]
RP CITRULLINATION AT ARG-9 AND ARG-18, AND METHYLATION AT ARG-18.
RX PubMed=15345777; DOI=10.1126/science.1101400;
RA Wang Y., Wysocka J., Sayegh J., Lee Y.-H., Perlin J.R., Leonelli L.,
RA Sonbuchner L.S., McDonald C.H., Cook R.G., Dou Y., Roeder R.G.,
RA Clarke S., Stallcup M.R., Allis C.D., Coonrod S.A.;
RT "Human PAD4 regulates histone arginine methylation levels via
RT demethylimination.";
RL Science 306:279-283(2004).
RN [23]
RP PHOSPHORYLATION AT THR-4; SER-11 AND SER-29.
RX PubMed=15681610; DOI=10.1101/gad.1267105;
RA Dai J., Sultan S., Taylor S.S., Higgins J.M.G.;
RT "The kinase haspin is required for mitotic histone H3 Thr 3
RT phosphorylation and normal metaphase chromosome alignment.";
RL Genes Dev. 19:472-488(2005).
RN [24]
RP PHOSPHORYLATION AT SER-29.
RX PubMed=15684425; DOI=10.1074/jbc.M410521200;
RA Choi H.S., Choi B.Y., Cho Y.-Y., Zhu F., Bode A.M., Dong Z.;
RT "Phosphorylation of Ser28 in histone H3 mediated by mixed lineage
RT kinase-like mitogen-activated protein triple kinase alpha.";
RL J. Biol. Chem. 280:13545-13553(2005).
RN [25]
RP METHYLATION AT LYS-37 AND LYS-38, AND MASS SPECTROMETRY.
RX PubMed=15983376; DOI=10.1073/pnas.0503189102;
RA Coon J.J., Ueberheide B., Syka J.E.P., Dryhurst D.D., Ausio J.,
RA Shabanowitz J., Hunt D.F.;
RT "Protein identification using sequential ion/ion reactions and tandem
RT mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:9463-9468(2005).
RN [26]
RP ACETYLATION AT LYS-10; LYS-15; LYS-19 AND LYS-24, METHYLATION AT
RP LYS-5; LYS-10; LYS-19; LYS-28; LYS-37; LYS-65; LYS-80 AND LYS-123, AND
RP MASS SPECTROMETRY.
RX PubMed=16267050; DOI=10.1074/jbc.M509266200;
RA Hake S.B., Garcia B.A., Duncan E.M., Kauer M., Dellaire G.,
RA Shabanowitz J., Bazett-Jones D.P., Allis C.D., Hunt D.F.;
RT "Expression patterns and post-translational modifications associated
RT with mammalian histone H3 variants.";
RL J. Biol. Chem. 281:559-568(2006).
RN [27]
RP METHYLATION AT LYS-5 AND LYS-10, ACETYLATION AT LYS-10; LYS-15 AND
RP LYS-24, PHOSPHORYLATION AT SER-11 AND SER-29, AND MASS SPECTROMETRY.
RX PubMed=16457588; DOI=10.1021/pr050266a;
RA Thomas C.E., Kelleher N.L., Mizzen C.A.;
RT "Mass spectrometric characterization of human histone H3: a bird's eye
RT view.";
RL J. Proteome Res. 5:240-247(2006).
RN [28]
RP UBIQUITINATION.
RX PubMed=16678110; DOI=10.1016/j.molcel.2006.03.035;
RA Wang H., Zhai L., Xu J., Joo H.-Y., Jackson S., Erdjument-Bromage H.,
RA Tempst P., Xiong Y., Zhang Y.;
RT "Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin
RT ligase facilitates cellular response to DNA damage.";
RL Mol. Cell 22:383-394(2006).
RN [29]
RP ACETYLATION AT LYS-10; LYS-15; LYS-19; LYS-24 AND LYS-28, METHYLATION
RP AT LYS-28; LYS-37 AND LYS-80, AND MASS SPECTROMETRY.
RX PubMed=16627869; DOI=10.1074/mcp.M600007-MCP200;
RA Beck H.C., Nielsen E.C., Matthiesen R., Jensen L.H., Sehested M.,
RA Finn P., Grauslund M., Hansen A.M., Jensen O.N.;
RT "Quantitative proteomic analysis of post-translational modifications
RT of human histones.";
RL Mol. Cell. Proteomics 5:1314-1325(2006).
RN [30]
RP ACETYLATION AT LYS-10 AND LYS-15, METHYLATION AT ARG-18, AND
RP CITRULLINATION AT ARG-18.
RX PubMed=16497732; DOI=10.1210/me.2005-0365;
RA Miao F., Li S., Chavez V., Lanting L., Natarajan R.;
RT "Coactivator-associated arginine methyltransferase-1 enhances nuclear
RT factor-kappaB-mediated gene transcription through methylation of
RT histone H3 at arginine 17.";
RL Mol. Endocrinol. 20:1562-1573(2006).
RN [31]
RP METHYLATION AT ARG-3 BY PRMT6.
RX PubMed=18079182; DOI=10.1101/gad.447007;
RA Hyllus D., Stein C., Schnabel K., Schiltz E., Imhof A., Dou Y.,
RA Hsieh J., Bauer U.M.;
RT "PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4
RT trimethylation.";
RL Genes Dev. 21:3369-3380(2007).
RN [32]
RP ACETYLATION AT LYS-5; LYS-10; LYS-15; LYS-19; LYS-24; LYS-28; LYS-37;
RP LYS-57 AND LYS-80, METHYLATION AT LYS-5; LYS-10; LYS-19; LYS-24;
RP LYS-28; LYS-37; LYS-57; LYS-65; LYS-80 AND LYS-123, AND MASS
RP SPECTROMETRY.
RX PubMed=17194708; DOI=10.1074/jbc.M607900200;
RA Garcia B.A., Hake S.B., Diaz R.L., Kauer M., Morris S.A., Recht J.,
RA Shabanowitz J., Mishra N., Strahl B.D., Allis C.D., Hunt D.F.;
RT "Organismal differences in post-translational modifications in
RT histones H3 and H4.";
RL J. Biol. Chem. 282:7641-7655(2007).
RN [33]
RP ACETYLATION AT LYS-37.
RX PubMed=17189264; DOI=10.1074/jbc.M607909200;
RA Morris S.A., Rao B., Garcia B.A., Hake S.B., Diaz R.L.,
RA Shabanowitz J., Hunt D.F., Allis C.D., Lieb J.D., Strahl B.D.;
RT "Identification of histone H3 lysine 36 acetylation as a highly
RT conserved histone modification.";
RL J. Biol. Chem. 282:7632-7640(2007).
RN [34]
RP METHYLATION AT ARG-3 BY PRMT6.
RX PubMed=17898714; DOI=10.1038/nature06166;
RA Guccione E., Bassi C., Casadio F., Martinato F., Cesaroni M.,
RA Schuchlautz H., Luescher B., Amati B.;
RT "Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are
RT mutually exclusive.";
RL Nature 449:933-937(2007).
RN [35]
RP PHOSPHORYLATION AT THR-12 BY CHEK1.
RX PubMed=18243098; DOI=10.1016/j.cell.2007.12.013;
RA Shimada M., Niida H., Zineldeen D.H., Tagami H., Tanaka M., Saito H.,
RA Nakanishi M.;
RT "Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-
RT induced transcriptional repression.";
RL Cell 132:221-232(2008).
RN [36]
RP METHYLATION AT ARG-3 BY PRMT6.
RX PubMed=18077460; DOI=10.1074/jbc.C700192200;
RA Iberg A.N., Espejo A., Cheng D., Kim D., Michaud-Levesque J.,
RA Richard S., Bedford M.T.;
RT "Arginine methylation of the histone H3 tail impedes effector
RT binding.";
RL J. Biol. Chem. 283:3006-3010(2008).
RN [37]
RP PHOSPHORYLATION AT THR-12.
RX PubMed=18066052; DOI=10.1038/ncb1668;
RA Metzger E., Yin N., Wissmann M., Kunowska N., Fischer K.,
RA Friedrichs N., Patnaik D., Higgins J.M., Potier N., Scheidtmann K.H.,
RA Buettner R., Schule R.;
RT "Phosphorylation of histone H3 at threonine 11 establishes a novel
RT chromatin mark for transcriptional regulation.";
RL Nat. Cell Biol. 10:53-60(2008).
RN [38]
RP ACETYLATION AT LYS-116 AND LYS-123.
RX PubMed=19520870; DOI=10.1074/jbc.M109.003202;
RA Manohar M., Mooney A.M., North J.A., Nakkula R.J., Picking J.W.,
RA Edon A., Fishel R., Poirier M.G., Ottesen J.J.;
RT "Acetylation of histone H3 at the nucleosome dyad alters DNA-histone
RT binding.";
RL J. Biol. Chem. 284:23312-23321(2009).
RN [39]
RP PHOSPHORYLATION AT TYR-42.
RX PubMed=19783980; DOI=10.1038/nature08448;
RA Dawson M.A., Bannister A.J., Gottgens B., Foster S.D., Bartke T.,
RA Green A.R., Kouzarides T.;
RT "JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from
RT chromatin.";
RL Nature 461:819-822(2009).
RN [40]
RP PHOSPHORYLATION AT SER-58 AND THR-81.
RX PubMed=20850016; DOI=10.1016/j.cell.2010.08.020;
RA Vermeulen M., Eberl H.C., Matarese F., Marks H., Denissov S.,
RA Butter F., Lee K.K., Olsen J.V., Hyman A.A., Stunnenberg H.G.,
RA Mann M.;
RT "Quantitative interaction proteomics and genome-wide profiling of
RT epigenetic histone marks and their readers.";
RL Cell 142:967-980(2010).
RN [41]
RP PHOSPHORYLATION AT THR-7.
RX PubMed=20228790; DOI=10.1038/nature08839;
RA Metzger E., Imhof A., Patel D., Kahl P., Hoffmeyer K., Friedrichs N.,
RA Muller J.M., Greschik H., Kirfel J., Ji S., Kunowska N.,
RA Beisenherz-Huss C., Gunther T., Buettner R., Schule R.;
RT "Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation
RT at histone H3K4.";
RL Nature 464:792-796(2010).
RN [42]
RP CROTONYLATION AT LYS-5; LYS-10; LYS-19; LYS-24; LYS-28 AND LYS-57.
RX PubMed=21925322; DOI=10.1016/j.cell.2011.08.008;
RA Tan M., Luo H., Lee S., Jin F., Yang J.S., Montellier E., Buchou T.,
RA Cheng Z., Rousseaux S., Rajagopal N., Lu Z., Ye Z., Zhu Q.,
RA Wysocka J., Ye Y., Khochbin S., Ren B., Zhao Y.;
RT "Identification of 67 histone marks and histone lysine crotonylation
RT as a new type of histone modification.";
RL Cell 146:1016-1028(2011).
RN [43]
RP METHYLATION AT LYS-57.
RX PubMed=22387026; DOI=10.1016/j.molcel.2012.01.019;
RA Yu Y., Song C., Zhang Q., Dimaggio P.A., Garcia B.A., York A.,
RA Carey M.F., Grunstein M.;
RT "Histone H3 lysine 56 methylation regulates DNA replication through
RT its interaction with PCNA.";
RL Mol. Cell 46:7-17(2012).
RN [44]
RP ALLYSINE AT LYS-5.
RX PubMed=22483618; DOI=10.1016/j.molcel.2012.03.002;
RA Herranz N., Dave N., Millanes-Romero A., Morey L., Diaz V.M.,
RA Lorenz-Fonfria V., Gutierrez-Gallego R., Jeronimo C., Di Croce L.,
RA Garcia de Herreros A., Peiro S.;
RT "Lysyl oxidase-like 2 deaminates lysine 4 in histone H3.";
RL Mol. Cell 46:369-376(2012).
RN [45]
RP ACETYLATION AT LYS-123.
RX PubMed=23415232; DOI=10.1016/j.cell.2013.01.032;
RA Tropberger P., Pott S., Keller C., Kamieniarz-Gdula K., Caron M.,
RA Richter F., Li G., Mittler G., Liu E.T., Buhler M., Margueron R.,
RA Schneider R.;
RT "Regulation of transcription through acetylation of H3K122 on the
RT lateral surface of the histone octamer.";
RL Cell 152:859-872(2013).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 8-15 IN COMPLEX WITH YWHAZ.
RX PubMed=16246723; DOI=10.1016/j.molcel.2005.08.032;
RA Macdonald N., Welburn J.P.I., Noble M.E.M., Nguyen A., Yaffe M.B.,
RA Clynes D., Moggs J.G., Orphanides G., Thomson S., Edmunds J.W.,
RA Clayton A.L., Endicott J.A., Mahadevan L.C.;
RT "Molecular basis for the recognition of phosphorylated and
RT phosphoacetylated histone h3 by 14-3-3.";
RL Mol. Cell 20:199-211(2005).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 2-20 IN COMPLEX WITH CHD1.
RX PubMed=16372014; DOI=10.1038/nature04290;
RA Flanagan J.F., Mi L.-Z., Chruszcz M., Cymborowski M., Clines K.L.,
RA Kim Y., Minor W., Rastinejad F., Khorasanizadeh S.;
RT "Double chromodomains cooperate to recognize the methylated histone H3
RT tail.";
RL Nature 438:1181-1185(2005).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=15951514; DOI=10.1093/nar/gki663;
RA Tsunaka Y., Kajimura N., Tate S., Morikawa K.;
RT "Alteration of the nucleosomal DNA path in the crystal structure of a
RT human nucleosome core particle.";
RL Nucleic Acids Res. 33:3424-3434(2005).
CC -!- FUNCTION: Core component of nucleosome. Nucleosomes wrap and
CC compact DNA into chromatin, limiting DNA accessibility to the
CC cellular machineries which require DNA as a template. Histones
CC thereby play a central role in transcription regulation, DNA
CC repair, DNA replication and chromosomal stability. DNA
CC accessibility is regulated via a complex set of post-translational
CC modifications of histones, also called histone code, and
CC nucleosome remodeling.
CC -!- SUBUNIT: The nucleosome is a histone octamer containing two
CC molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4
CC heterotetramer and two H2A-H2B heterodimers. The octamer wraps
CC approximately 147 bp of DNA.
CC -!- INTERACTION:
CC O43918:AIRE; NbExp=20; IntAct=EBI-79722, EBI-1753081;
CC P83916:CBX1; NbExp=9; IntAct=EBI-79722, EBI-78129;
CC Q13185:CBX3; NbExp=5; IntAct=EBI-79722, EBI-78176;
CC P45973:CBX5; NbExp=9; IntAct=EBI-79722, EBI-78219;
CC Q96ES7:CCDC101; NbExp=25; IntAct=EBI-79722, EBI-743117;
CC Q9Y232:CDYL; NbExp=5; IntAct=EBI-79722, EBI-1387386;
CC P42858:HTT; NbExp=2; IntAct=EBI-79722, EBI-466029;
CC Q9UNL4:ING4; NbExp=3; IntAct=EBI-79722, EBI-2866661;
CC P38991:IPL1 (xeno); NbExp=2; IntAct=EBI-79722, EBI-9319;
CC O75164:KDM4A; NbExp=7; IntAct=EBI-79722, EBI-936709;
CC Q03164:KMT2A; NbExp=11; IntAct=EBI-79722, EBI-591370;
CC Q9Y468:L3MBTL1; NbExp=2; IntAct=EBI-79722, EBI-1265089;
CC Q99549:MPHOSPH8; NbExp=5; IntAct=EBI-79722, EBI-2653928;
CC Q9BVI0:PHF20; NbExp=6; IntAct=EBI-79722, EBI-2560802;
CC A8MW92:PHF20L1; NbExp=2; IntAct=EBI-79722, EBI-2560834;
CC Q8WTS6:SETD7; NbExp=4; IntAct=EBI-79722, EBI-1268586;
CC P25554:SGF29 (xeno); NbExp=11; IntAct=EBI-79722, EBI-21678;
CC Q12888:TP53BP1; NbExp=5; IntAct=EBI-79722, EBI-396540;
CC P61964:WDR5; NbExp=9; IntAct=EBI-79722, EBI-540834;
CC P63104:YWHAZ; NbExp=3; IntAct=EBI-79722, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC -!- DEVELOPMENTAL STAGE: Expressed during S phase, then expression
CC strongly decreases as cell division slows down during the process
CC of differentiation.
CC -!- PTM: Acetylation is generally linked to gene activation.
CC Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9
CC (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac)
CC favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123
CC (H3K122ac) by EP300/p300 plays a central role in chromatin
CC structure: localizes at the surface of the histone octamer and
CC stimulates transcription, possibly by promoting nucleosome
CC instability.
CC -!- PTM: Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by
CC PADI4 impairs methylation and represses transcription.
CC -!- PTM: Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is
CC linked to gene activation. Symmetric dimethylation at Arg-9
CC (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric
CC dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene
CC repression and is mutually exclusive with H3 Lys-5 methylation
CC (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes
CC regardless of their transcription state and is enriched on
CC inactive promoters, while it is absent on active promoters.
CC -!- PTM: Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80
CC (H3K79me) are linked to gene activation. Methylation at Lys-5
CC (H3K4me) facilitates subsequent acetylation of H3 and H4.
CC Methylation at Lys-80 (H3K79me) is associated with DNA double-
CC strand break (DSB) responses and is a specific target for TP53BP1.
CC Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to
CC gene repression. Methylation at Lys-10 (H3K9me) is a specific
CC target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents
CC subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of
CC H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me)
CC require preliminary monoubiquitination of H2B at 'Lys-120'.
CC Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched
CC in inactive X chromosome chromatin. Monomethylation at Lys-57
CC (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA
CC and is required for DNA replication.
CC -!- PTM: Phosphorylated at Thr-4 (H3T3ph) by GSG2/haspin during
CC prophase and dephosphorylated during anaphase. Phosphorylation at
CC Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation
CC and cell-cycle progression during mitosis and meiosis. In addition
CC phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is
CC important during interphase because it enables the transcription
CC of genes following external stimulation, like mitogens, stress,
CC growth factors or UV irradiation and result in the activation of
CC genes, such as c-fos and c-jun. Phosphorylation at Ser-11
CC (H3S10ph), which is linked to gene activation, prevents
CC methylation at Lys-10 (H3K9me) but facilitates acetylation of H3
CC and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the
CC dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from
CC heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an
CC essential regulatory mechanism for neoplastic cell transformation.
CC Phosphorylated at Ser-29 (H3S28ph) by MLTK isoform 1, RPS6KA5 or
CC AURKB during mitosis or upon ultraviolet B irradiation.
CC Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for
CC epigenetic transcriptional activation that prevents demethylation
CC of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically
CC phosphorylated at Thr-12 (H3T11ph) from prophase to early
CC anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph)
CC by PKN1 is a specific tag for epigenetic transcriptional
CC activation that promotes demethylation of Lys-10 (H3K9me) by
CC KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-
CC associated CHEK1 regulates the transcription of cell cycle
CC regulatory genes by modulating acetylation of Lys-10 (H3K9ac).
CC Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of
CC CBX5 (HP1 alpha) from chromatin.
CC -!- PTM: Monoubiquitinated by RAG1 in lymphoid cells,
CC monoubiquitination is required for V(D)J recombination (By
CC similarity). Ubiquitinated by the CUL4-DDB-RBX1 complex in
CC response to ultraviolet irradiation. This may weaken the
CC interaction between histones and DNA and facilitate DNA
CC accessibility to repair proteins.
CC -!- PTM: Lysine deamination at Lys-5 (H3K4all) to form allysine is
CC mediated by LOXL2. Allysine formation by LOXL2 only takes place on
CC H3K4me3 and results in gene repression (PubMed:22483618).
CC -!- PTM: Crotonylation (Kcr) is specifically present in male germ
CC cells and marks testis-specific genes in post-meiotic cells,
CC including X-linked genes that escape sex chromosome inactivation
CC in haploid cells. Crotonylation marks active promoters and
CC enhancers and confers resistance to transcriptional repressors. It
CC is also associated with post-meiotically activated genes on
CC autosomes.
CC -!- MISCELLANEOUS: This histone is only present in mammals and is
CC enriched in acetylation of Lys-15 and dimethylation of Lys-10
CC (H3K9me2).
CC -!- SIMILARITY: Belongs to the histone H3 family.
CC -----------------------------------------------------------------------
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DR EMBL; X00090; CAA24952.1; -; Genomic_DNA.
DR EMBL; M26150; AAA52651.1; -; Genomic_DNA.
DR EMBL; M60746; AAA63185.1; -; Genomic_DNA.
DR EMBL; X57128; CAA40407.1; -; Genomic_DNA.
DR EMBL; Z46261; CAA86403.1; -; Genomic_DNA.
DR EMBL; X83550; CAA58540.1; -; Genomic_DNA.
DR EMBL; Z80784; CAB02546.1; -; Genomic_DNA.
DR EMBL; Z80785; CAB02547.1; -; Genomic_DNA.
DR EMBL; Z80786; CAB02548.1; -; Genomic_DNA.
DR EMBL; Z83735; CAB06030.1; -; Genomic_DNA.
DR EMBL; Z83737; CAB06032.1; -; Genomic_DNA.
DR EMBL; AF531274; AAN10051.1; -; Genomic_DNA.
DR EMBL; AF531275; AAN10052.1; -; Genomic_DNA.
DR EMBL; AF531276; AAN10053.1; -; Genomic_DNA.
DR EMBL; AF531277; AAN10054.1; -; Genomic_DNA.
DR EMBL; AF531278; AAN10055.1; -; Genomic_DNA.
DR EMBL; AF531279; AAN10056.1; -; Genomic_DNA.
DR EMBL; AF531280; AAN10057.1; -; Genomic_DNA.
DR EMBL; AF531281; AAN10058.1; -; Genomic_DNA.
DR EMBL; AF531282; AAN10059.1; -; Genomic_DNA.
DR EMBL; AF531283; AAN10060.1; -; Genomic_DNA.
DR EMBL; AK311991; BAG34929.1; -; mRNA.
DR EMBL; AK313905; BAG36628.1; -; mRNA.
DR EMBL; AK314142; BAG36832.1; -; mRNA.
DR EMBL; AK316611; BAG38198.1; -; mRNA.
DR EMBL; CR542014; CAG46811.1; -; mRNA.
DR EMBL; CR542011; CAG46808.1; -; mRNA.
DR EMBL; CR541983; CAG46780.1; -; mRNA.
DR EMBL; CR541858; CAG46656.1; -; mRNA.
DR EMBL; Z98744; CAD24076.1; -; Genomic_DNA.
DR EMBL; Z98744; CAB11424.1; -; Genomic_DNA.
DR EMBL; AL009179; CAA15670.1; -; Genomic_DNA.
DR EMBL; AL031777; CAC03412.1; -; Genomic_DNA.
DR EMBL; AL031777; CAC03413.1; -; Genomic_DNA.
DR EMBL; AL031777; CAC03416.1; -; Genomic_DNA.
DR EMBL; AL031777; CAC03421.1; -; Genomic_DNA.
DR EMBL; BC031333; AAH31333.1; -; mRNA.
DR EMBL; BC066245; AAH66245.1; -; mRNA.
DR EMBL; BC066246; AAH66246.1; -; mRNA.
DR EMBL; BC066247; AAH66247.1; -; mRNA.
DR EMBL; BC066884; AAH66884.1; -; mRNA.
DR EMBL; BC067490; AAH67490.1; -; mRNA.
DR EMBL; BC067491; AAH67491.1; -; mRNA.
DR EMBL; BC067492; AAH67492.1; -; mRNA.
DR EMBL; BC067493; AAH67493.1; -; mRNA.
DR EMBL; BC069133; AAH69133.1; -; mRNA.
DR EMBL; BC069303; AAH69303.1; -; mRNA.
DR EMBL; BC069305; AAH69305.2; -; mRNA.
DR EMBL; BC069818; AAH69818.1; -; mRNA.
DR EMBL; BC096128; AAH96128.1; -; mRNA.
DR EMBL; BC096129; AAH96129.1; -; mRNA.
DR EMBL; BC096130; AAH96130.1; -; mRNA.
DR EMBL; BC096131; AAH96131.1; -; mRNA.
DR EMBL; BC096132; AAH96132.1; -; mRNA.
DR EMBL; BC096133; AAH96133.1; -; mRNA.
DR EMBL; BC096134; AAH96134.1; -; mRNA.
DR EMBL; BC099630; AAH99630.1; -; mRNA.
DR EMBL; BC127610; AAI27611.1; -; mRNA.
DR EMBL; BC143046; AAI43047.1; -; mRNA.
DR EMBL; BC148243; AAI48244.1; -; mRNA.
DR EMBL; BC148250; AAI48251.1; -; mRNA.
DR PIR; I37446; HSHU3.
DR RefSeq; NP_003520.1; NM_003529.2.
DR RefSeq; NP_003521.2; NM_003530.4.
DR RefSeq; NP_003522.1; NM_003531.2.
DR RefSeq; NP_003523.1; NM_003532.2.
DR RefSeq; NP_003524.1; NM_003533.2.
DR RefSeq; NP_003525.1; NM_003534.2.
DR RefSeq; NP_003526.1; NM_003535.2.
DR RefSeq; NP_003527.1; NM_003536.2.
DR RefSeq; NP_003528.1; NM_003537.3.
DR RefSeq; NP_066298.1; NM_021018.2.
DR RefSeq; XP_005249499.1; XM_005249442.1.
DR RefSeq; XP_005249500.1; XM_005249443.1.
DR UniGene; Hs.132854; -.
DR UniGene; Hs.247813; -.
DR UniGene; Hs.247814; -.
DR UniGene; Hs.248176; -.
DR UniGene; Hs.443021; -.
DR UniGene; Hs.484990; -.
DR UniGene; Hs.532144; -.
DR UniGene; Hs.533292; -.
DR UniGene; Hs.546315; -.
DR UniGene; Hs.586261; -.
DR UniGene; Hs.591778; -.
DR UniGene; Hs.626666; -.
DR PDB; 1CS9; NMR; -; A=131-136.
DR PDB; 1CT6; NMR; -; A=131-135.
DR PDB; 1Q3L; X-ray; 1.64 A; P=2-16.
DR PDB; 2B2T; X-ray; 2.45 A; D=2-20.
DR PDB; 2B2U; X-ray; 2.95 A; D=4-16.
DR PDB; 2B2V; X-ray; 2.65 A; D=2-16.
DR PDB; 2B2W; X-ray; 2.40 A; D=2-20.
DR PDB; 2C1J; X-ray; 2.60 A; C/D=8-15.
DR PDB; 2C1N; X-ray; 2.00 A; C/E=8-15.
DR PDB; 2CV5; X-ray; 2.50 A; A/E=1-136.
DR PDB; 2KWJ; NMR; -; B=2-21.
DR PDB; 2KWK; NMR; -; B=2-21.
DR PDB; 2L75; NMR; -; B=2-14.
DR PDB; 2LBM; NMR; -; C=2-16.
DR PDB; 2M0O; NMR; -; B=32-42.
DR PDB; 2RI7; X-ray; 1.45 A; P=2-10.
DR PDB; 2UXN; X-ray; 2.72 A; E=2-22.
DR PDB; 2VPG; X-ray; 1.60 A; P/R=2-19.
DR PDB; 3A1B; X-ray; 2.29 A; A=2-21.
DR PDB; 3AFA; X-ray; 2.50 A; A/E=1-136.
DR PDB; 3AVR; X-ray; 1.80 A; B=18-39.
DR PDB; 3AYW; X-ray; 2.90 A; A/E=1-136.
DR PDB; 3AZE; X-ray; 3.00 A; A/E=1-136.
DR PDB; 3AZF; X-ray; 2.70 A; A/E=1-136.
DR PDB; 3AZG; X-ray; 2.40 A; A/E=1-136.
DR PDB; 3AZH; X-ray; 3.49 A; A/E=1-136.
DR PDB; 3AZI; X-ray; 2.70 A; A/E=1-136.
DR PDB; 3AZJ; X-ray; 2.89 A; A/E=1-136.
DR PDB; 3AZK; X-ray; 3.20 A; A/E=1-136.
DR PDB; 3AZL; X-ray; 2.70 A; A/E=1-136.
DR PDB; 3AZM; X-ray; 2.89 A; A/E=1-136.
DR PDB; 3AZN; X-ray; 3.00 A; A/E=1-136.
DR PDB; 3B95; X-ray; 2.99 A; P=2-16.
DR PDB; 3KMT; X-ray; 1.78 A; G/H/I=26-33.
DR PDB; 3KQI; X-ray; 1.78 A; B=2-13.
DR PDB; 3LQI; X-ray; 1.92 A; R/S/T=2-10.
DR PDB; 3LQJ; X-ray; 1.90 A; Q/T=2-10.
DR PDB; 3O34; X-ray; 1.90 A; B=14-33.
DR PDB; 3O35; X-ray; 1.76 A; D/E=24-32.
DR PDB; 3O37; X-ray; 2.00 A; E/F/G/H=2-11.
DR PDB; 3RIG; X-ray; 2.00 A; C/D=5-16.
DR PDB; 3RIY; X-ray; 1.55 A; C/D=5-16.
DR PDB; 3U4S; X-ray; 2.15 A; C/D=8-15.
DR PDB; 3U5N; X-ray; 1.95 A; C/D=2-21.
DR PDB; 3U5O; X-ray; 2.70 A; I/J/K/L/M/N/O/P=2-23.
DR PDB; 3U5P; X-ray; 2.80 A; I/J/K/L/M/N/O/P=2-29.
DR PDB; 3UEE; X-ray; 2.61 A; B/D=2-13.
DR PDB; 3UEF; X-ray; 2.45 A; B/D=2-13.
DR PDB; 3UIG; X-ray; 2.40 A; P/Q=2-16.
DR PDB; 3UII; X-ray; 2.60 A; P/Q=2-11.
DR PDB; 3UIK; X-ray; 2.70 A; P/Q=2-11.
DR PDB; 3V43; X-ray; 1.47 A; Q=2-19.
DR PDB; 3W96; X-ray; 3.00 A; A/E=1-136.
DR PDB; 3W97; X-ray; 3.20 A; A/E=1-136.
DR PDB; 3W98; X-ray; 3.42 A; A/E=29-136.
DR PDB; 3W99; X-ray; 3.00 A; A/E=1-136.
DR PDB; 3ZG6; X-ray; 2.20 A; F=5-14.
DR PDB; 3ZVY; X-ray; 1.95 A; C/D=2-9.
DR PDB; 4A0J; X-ray; 2.80 A; C/D=2-7.
DR PDB; 4A0N; X-ray; 2.74 A; C=2-7.
DR PDB; 4A7J; X-ray; 1.90 A; B=1-16.
DR PDB; 4BD3; NMR; -; B=32-42.
DR PDB; 4C1Q; X-ray; 2.30 A; C=2-10.
DR PDB; 4F4U; X-ray; 2.00 A; C/D=5-16.
DR PDB; 4F56; X-ray; 1.70 A; C/D=5-16.
DR PDB; 4FWF; X-ray; 2.70 A; E=2-21.
DR PDB; 4HON; X-ray; 1.80 A; F/G=7-16.
DR PDB; 4I51; X-ray; 1.90 A; C/D=4-12.
DR PDB; 4L7X; X-ray; 1.35 A; U=2-13.
DR PDB; 4LK9; X-ray; 1.60 A; B=2-22.
DR PDB; 4LKA; X-ray; 1.61 A; B=2-22.
DR PDB; 4LLB; X-ray; 2.50 A; C/D=2-22.
DR PDBsum; 1CS9; -.
DR PDBsum; 1CT6; -.
DR PDBsum; 1Q3L; -.
DR PDBsum; 2B2T; -.
DR PDBsum; 2B2U; -.
DR PDBsum; 2B2V; -.
DR PDBsum; 2B2W; -.
DR PDBsum; 2C1J; -.
DR PDBsum; 2C1N; -.
DR PDBsum; 2CV5; -.
DR PDBsum; 2KWJ; -.
DR PDBsum; 2KWK; -.
DR PDBsum; 2L75; -.
DR PDBsum; 2LBM; -.
DR PDBsum; 2M0O; -.
DR PDBsum; 2RI7; -.
DR PDBsum; 2UXN; -.
DR PDBsum; 2VPG; -.
DR PDBsum; 3A1B; -.
DR PDBsum; 3AFA; -.
DR PDBsum; 3AVR; -.
DR PDBsum; 3AYW; -.
DR PDBsum; 3AZE; -.
DR PDBsum; 3AZF; -.
DR PDBsum; 3AZG; -.
DR PDBsum; 3AZH; -.
DR PDBsum; 3AZI; -.
DR PDBsum; 3AZJ; -.
DR PDBsum; 3AZK; -.
DR PDBsum; 3AZL; -.
DR PDBsum; 3AZM; -.
DR PDBsum; 3AZN; -.
DR PDBsum; 3B95; -.
DR PDBsum; 3KMT; -.
DR PDBsum; 3KQI; -.
DR PDBsum; 3LQI; -.
DR PDBsum; 3LQJ; -.
DR PDBsum; 3O34; -.
DR PDBsum; 3O35; -.
DR PDBsum; 3O37; -.
DR PDBsum; 3RIG; -.
DR PDBsum; 3RIY; -.
DR PDBsum; 3U4S; -.
DR PDBsum; 3U5N; -.
DR PDBsum; 3U5O; -.
DR PDBsum; 3U5P; -.
DR PDBsum; 3UEE; -.
DR PDBsum; 3UEF; -.
DR PDBsum; 3UIG; -.
DR PDBsum; 3UII; -.
DR PDBsum; 3UIK; -.
DR PDBsum; 3V43; -.
DR PDBsum; 3W96; -.
DR PDBsum; 3W97; -.
DR PDBsum; 3W98; -.
DR PDBsum; 3W99; -.
DR PDBsum; 3ZG6; -.
DR PDBsum; 3ZVY; -.
DR PDBsum; 4A0J; -.
DR PDBsum; 4A0N; -.
DR PDBsum; 4A7J; -.
DR PDBsum; 4BD3; -.
DR PDBsum; 4C1Q; -.
DR PDBsum; 4F4U; -.
DR PDBsum; 4F56; -.
DR PDBsum; 4FWF; -.
DR PDBsum; 4HON; -.
DR PDBsum; 4I51; -.
DR PDBsum; 4L7X; -.
DR PDBsum; 4LK9; -.
DR PDBsum; 4LKA; -.
DR PDBsum; 4LLB; -.
DR ProteinModelPortal; P68431; -.
DR SMR; P68431; 17-136.
DR DIP; DIP-29371N; -.
DR IntAct; P68431; 53.
DR MINT; MINT-256465; -.
DR PhosphoSite; P68431; -.
DR PaxDb; P68431; -.
DR PRIDE; P68431; -.
DR DNASU; 8350; -.
DR DNASU; 8352; -.
DR DNASU; 8353; -.
DR DNASU; 8355; -.
DR DNASU; 8356; -.
DR DNASU; 8357; -.
DR Ensembl; ENST00000244661; ENSP00000244661; ENSG00000124693.
DR Ensembl; ENST00000305910; ENSP00000439660; ENSG00000256018.
DR Ensembl; ENST00000328488; ENSP00000329554; ENSG00000182572.
DR Ensembl; ENST00000356476; ENSP00000366999; ENSG00000197409.
DR Ensembl; ENST00000357647; ENSP00000350275; ENSG00000198366.
DR Ensembl; ENST00000359303; ENSP00000352252; ENSG00000197153.
DR Ensembl; ENST00000360408; ENSP00000353581; ENSG00000196966.
DR Ensembl; ENST00000369163; ENSP00000358160; ENSG00000203813.
DR Ensembl; ENST00000377831; ENSP00000367062; ENSG00000197409.
DR Ensembl; ENST00000446824; ENSP00000444823; ENSG00000256316.
DR Ensembl; ENST00000540144; ENSP00000439493; ENSG00000196532.
DR GeneID; 8350; -.
DR GeneID; 8351; -.
DR GeneID; 8352; -.
DR GeneID; 8353; -.
DR GeneID; 8354; -.
DR GeneID; 8355; -.
DR GeneID; 8356; -.
DR GeneID; 8357; -.
DR GeneID; 8358; -.
DR GeneID; 8968; -.
DR KEGG; hsa:8350; -.
DR KEGG; hsa:8351; -.
DR KEGG; hsa:8352; -.
DR KEGG; hsa:8353; -.
DR KEGG; hsa:8354; -.
DR KEGG; hsa:8355; -.
DR KEGG; hsa:8356; -.
DR KEGG; hsa:8357; -.
DR KEGG; hsa:8358; -.
DR KEGG; hsa:8968; -.
DR UCSC; uc003nfp.1; human.
DR CTD; 8350; -.
DR CTD; 8351; -.
DR CTD; 8352; -.
DR CTD; 8353; -.
DR CTD; 8354; -.
DR CTD; 8355; -.
DR CTD; 8356; -.
DR CTD; 8357; -.
DR CTD; 8358; -.
DR CTD; 8968; -.
DR GeneCards; GC06M026031; -.
DR GeneCards; GC06M026197; -.
DR GeneCards; GC06M026250; -.
DR GeneCards; GC06M026271; -.
DR GeneCards; GC06M027914; -.
DR GeneCards; GC06M027920; -.
DR GeneCards; GC06P026020; -.
DR GeneCards; GC06P026065; -.
DR GeneCards; GC06P026225; -.
DR GeneCards; GC06P027777; -.
DR HGNC; HGNC:4766; HIST1H3A.
DR HGNC; HGNC:4776; HIST1H3B.
DR HGNC; HGNC:4768; HIST1H3C.
DR HGNC; HGNC:4767; HIST1H3D.
DR HGNC; HGNC:4769; HIST1H3E.
DR HGNC; HGNC:4773; HIST1H3F.
DR HGNC; HGNC:4772; HIST1H3G.
DR HGNC; HGNC:4775; HIST1H3H.
DR HGNC; HGNC:4771; HIST1H3I.
DR HGNC; HGNC:4774; HIST1H3J.
DR HPA; CAB037166; -.
DR HPA; CAB037178; -.
DR HPA; CAB037187; -.
DR MIM; 602810; gene.
DR MIM; 602811; gene.
DR MIM; 602812; gene.
DR MIM; 602813; gene.
DR MIM; 602814; gene.
DR MIM; 602815; gene.
DR MIM; 602816; gene.
DR MIM; 602817; gene.
DR MIM; 602818; gene.
DR MIM; 602819; gene.
DR neXtProt; NX_P68431; -.
DR PharmGKB; PA29148; -.
DR eggNOG; COG2036; -.
DR HOVERGEN; HBG001172; -.
DR InParanoid; P68431; -.
DR KO; K11253; -.
DR OMA; EARSHQE; -.
DR OrthoDB; EOG7HB5C2; -.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_120956; Cellular responses to stress.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; HIST1H3F; human.
DR EvolutionaryTrace; P68431; -.
DR GeneWiki; HIST1H3A; -.
DR GeneWiki; HIST1H3B; -.
DR GeneWiki; HIST1H3C; -.
DR GeneWiki; HIST1H3D; -.
DR GeneWiki; HIST1H3E; -.
DR GeneWiki; HIST1H3F; -.
DR GeneWiki; HIST1H3G; -.
DR GeneWiki; HIST1H3H; -.
DR GeneWiki; HIST1H3I; -.
DR GeneWiki; HIST1H3J; -.
DR NextBio; 31272; -.
DR Bgee; P68431; -.
DR CleanEx; HS_HIST1H3A; -.
DR CleanEx; HS_HIST1H3B; -.
DR CleanEx; HS_HIST1H3C; -.
DR CleanEx; HS_HIST1H3D; -.
DR CleanEx; HS_HIST1H3E; -.
DR CleanEx; HS_HIST1H3F; -.
DR CleanEx; HS_HIST1H3G; -.
DR CleanEx; HS_HIST1H3H; -.
DR CleanEx; HS_HIST1H3I; -.
DR Genevestigator; P68431; -.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000786; C:nucleosome; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0006334; P:nucleosome assembly; IEA:InterPro.
DR GO; GO:0060968; P:regulation of gene silencing; IDA:BHF-UCL.
DR Gene3D; 1.10.20.10; -; 1.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR007125; Histone_core_D.
DR InterPro; IPR000164; Histone_H3.
DR PANTHER; PTHR11426; PTHR11426; 1.
DR Pfam; PF00125; Histone; 1.
DR PRINTS; PR00622; HISTONEH3.
DR SMART; SM00428; H3; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR PROSITE; PS00322; HISTONE_H3_1; 1.
DR PROSITE; PS00959; HISTONE_H3_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosome; Citrullination;
KW Complete proteome; Direct protein sequencing; DNA-binding;
KW Methylation; Nucleosome core; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 136 Histone H3.1.
FT /FTId=PRO_0000221245.
FT MOD_RES 3 3 Asymmetric dimethylarginine; by PRMT6.
FT MOD_RES 4 4 Phosphothreonine; by GSG2.
FT MOD_RES 5 5 Allysine; alternate.
FT MOD_RES 5 5 N6,N6,N6-trimethyllysine; alternate.
FT MOD_RES 5 5 N6,N6-dimethyllysine; alternate.
FT MOD_RES 5 5 N6-acetyllysine; alternate.
FT MOD_RES 5 5 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 5 5 N6-methyllysine; alternate.
FT MOD_RES 7 7 Phosphothreonine; by PKC.
FT MOD_RES 9 9 Citrulline; alternate.
FT MOD_RES 9 9 Symmetric dimethylarginine; by PRMT5;
FT alternate (By similarity).
FT MOD_RES 10 10 N6,N6,N6-trimethyllysine; alternate.
FT MOD_RES 10 10 N6,N6-dimethyllysine; alternate.
FT MOD_RES 10 10 N6-acetyllysine; alternate.
FT MOD_RES 10 10 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 10 10 N6-methyllysine; alternate.
FT MOD_RES 11 11 Phosphoserine; by AURKB, AURKC, RPS6KA3,
FT RPS6KA4 and RPS6KA5.
FT MOD_RES 12 12 Phosphothreonine; by PKC and CHEK1.
FT MOD_RES 15 15 N6-acetyllysine.
FT MOD_RES 18 18 Asymmetric dimethylarginine; by CARM1;
FT alternate.
FT MOD_RES 18 18 Citrulline; alternate.
FT MOD_RES 19 19 N6-acetyllysine; alternate.
FT MOD_RES 19 19 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 19 19 N6-methyllysine; alternate.
FT MOD_RES 24 24 N6-acetyllysine; alternate.
FT MOD_RES 24 24 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 24 24 N6-methyllysine; alternate.
FT MOD_RES 28 28 N6,N6,N6-trimethyllysine; alternate.
FT MOD_RES 28 28 N6,N6-dimethyllysine; alternate.
FT MOD_RES 28 28 N6-acetyllysine; alternate.
FT MOD_RES 28 28 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 28 28 N6-methyllysine; alternate.
FT MOD_RES 29 29 Phosphoserine; by AURKB, AURKC and
FT RPS6KA5.
FT MOD_RES 37 37 N6,N6,N6-trimethyllysine; alternate.
FT MOD_RES 37 37 N6,N6-dimethyllysine; alternate.
FT MOD_RES 37 37 N6-acetyllysine; alternate.
FT MOD_RES 37 37 N6-methyllysine; alternate.
FT MOD_RES 38 38 N6-methyllysine.
FT MOD_RES 42 42 Phosphotyrosine.
FT MOD_RES 57 57 N6,N6,N6-trimethyllysine; alternate.
FT MOD_RES 57 57 N6-acetyllysine; alternate.
FT MOD_RES 57 57 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 57 57 N6-methyllysine; by EHMT2; alternate.
FT MOD_RES 58 58 Phosphoserine.
FT MOD_RES 65 65 N6-methyllysine.
FT MOD_RES 80 80 N6,N6,N6-trimethyllysine; alternate (By
FT similarity).
FT MOD_RES 80 80 N6,N6-dimethyllysine; alternate.
FT MOD_RES 80 80 N6-acetyllysine; alternate.
FT MOD_RES 80 80 N6-methyllysine; alternate.
FT MOD_RES 81 81 Phosphothreonine.
FT MOD_RES 108 108 Phosphothreonine (By similarity).
FT MOD_RES 116 116 N6-acetyllysine.
FT MOD_RES 123 123 N6-acetyllysine; alternate.
FT MOD_RES 123 123 N6-methyllysine; alternate.
FT CONFLICT 70 70 R -> C (in Ref. 13; AAH67493).
FT CONFLICT 100 100 Y -> T (in Ref. 7; CAB02546).
FT CONFLICT 122 122 P -> L (in Ref. 13; AAH66884).
FT CONFLICT 135 135 Missing (in Ref. 2; AAA52651).
FT TURN 5 7
FT STRAND 14 16
FT HELIX 46 57
FT HELIX 65 77
FT STRAND 80 82
FT HELIX 87 114
FT STRAND 118 120
FT HELIX 122 131
SQ SEQUENCE 136 AA; 15404 MW; 9B89008EA50A0EF6 CRC64;
MARTKQTARK STGGKAPRKQ LATKAARKSA PATGGVKKPH RYRPGTVALR EIRRYQKSTE
LLIRKLPFQR LVREIAQDFK TDLRFQSSAV MALQEACEAY LVGLFEDTNL CAIHAKRVTI
MPKDIQLARR IRGERA
//

MIM 602810
*RECORD*
*FIELD* NO
602810
*FIELD* TI
*602810 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER A; HIST1H3A
;;HISTONE GENE CLUSTER 1, H3A;;
read moreHIST1 CLUSTER, H3A;;
H3 HISTONE FAMILY, MEMBER A; H3FA;;
H3/A
*FIELD* TX

DESCRIPTION

Histones are small, highly basic proteins that consist of a globular
domain with unstructured N- and C-terminal tails protruding from the
main structure. The histone family contains the core histones H2A (see
613499), H2B (see 609904), H3, and H4 (see 602822) and the linker
histone H1 (see 142709). Two full turns of eukaryotic DNA are tightly
packaged and ordered in nucleosomes, which consist of an octamer formed
by 2 each of the core histones. Nucleosomes are the fundamental unit of
chromatin. Histone H1 binds the linker DNA between nucleosomes, thereby
increasing the overall stability of chromatin by forming higher order
structures. In addition to their role in DNA compartmentalization,
histones also play crucial roles in various biologic processes,
including gene expression and regulation, DNA repair, chromatin
condensation, cell cycle progression, chromosome segregation, and
apoptosis. The ability of histones to regulate chromatin dynamics
primarily originates from various posttranslational modifications
carried out by histone-modifying enzymes. HIST1H3A is a core histone H3
(summary by Marzluff et al. (2002) and Healy et al. (2012)).

For additional background information on histones, histone gene
clusters, and the H3 histone family, see GENE FAMILY below.

GENE FAMILY

Like other histones, H3 histones can be subgrouped according to their
temporal expression. Replication-dependent histones, such as HIST1H3A
through HIST1H3J (602817), HIST2H3C (142780), and HIST3H3 (602820) are
mainly expressed during S phase. In contrast, replication-independent
histones, or replacement variant histones, such as H3F3A (601128) and
H3F3B (601058), can be expressed throughout the cell cycle. Most
replication-dependent H3 histone genes, as well as other core histone
genes, are located within histone gene cluster-1 (HIST1) on chromosome
6p22-p21. Two other histone gene clusters, HIST2 and HIST3, are located
on chromosomes 1q21 and 1q42, respectively, and each contains at least 1
replication-dependent H3 histone gene. In mouse, the Hist1, Hist2, and
Hist3 gene clusters are located on chromosomes 13A2-A3, 3F1-F2, and
11B2, respectively. All replication-dependent histone genes are
intronless, and they encode mRNAs that lack a poly(A) tail, ending
instead in a conserved stem-loop sequence. Unlike replication-dependent
histone genes, replication-independent histone genes are solitary genes
that are located on chromosomes apart from any other H1 or core histone
genes. Some replication-independent histone genes contain introns and
encode mRNAs with poly(A) tails. All H3 histone genes in the HIST1
cluster encode the same protein, designated H3.1. The H3 histone gene in
the HIST2 cluster, HIST2H3C, encodes a protein designated H3.2, which
differs from H3.1 only at residue 96, which is a cysteine in H3.1 and a
serine in H3.2. The H3 histone gene in the HIST3 cluster, HIST3H3,
encodes a protein that contains ser96 and 4 other changes relative to
H3.1 and H3.2. The replication-independent H3 histone genes, H3F3A and
H3F3B, encode the same protein, designated H3.3, which is distinct from
H3.1 and H3.2 (summary by Marzluff et al. (2002)).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3A genes. They noted that all H3 genes in the
HIST1 cluster, including HIST1H3A, encode the same protein, designated
H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C (142780), at
only 1 residue, and from histone H3.3, which is encoded by both H3F3A
(601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes that included H3/a.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
HIST1 cluster on chromosome 6p22-p21 contains 55 histone genes,
including 10 H3 genes. The HIST1H3A gene is the most telomeric H3 gene
within the HIST1 cluster. The HIST1 cluster spans over 2 Mb and includes
2 large gaps (over 250 kb each) where there are no histone genes, but
many other genes. The organization of histone genes in the mouse Hist1
cluster on chromosome 13A2-A3 is essentially identical to that in human
HIST1. The HIST2 cluster on chromosome 1q21 contains 6 histone genes,
including 1 H3 gene (HIST2H3C; 142780), and the HIST3 cluster on
chromosome 1q42 contains 3 histone genes, including 1 H3 gene (HIST3H3;
602820). Hist2 and Hist3 are located on mouse chromosomes 3F1-F2 and
11B2, respectively.

GENE FUNCTION

- H3.1 Histone

Hake et al. (2006) noted that most studies on expression or
posttranslational modifications of H3 histones do not differentiate
between the H3.1, H3.2, and H3.3 proteins, in part due to their high
degree of amino acid identity. By quantitative PCR of 5 human cell
lines, they found that the 9 H3.1 genes, 1 H3.2 gene, and 2 H3.3 genes
examined were expressed in a cell line-specific manner. All 3 types of
H3 genes were highly expressed during S phase in human cell lines,
whereas the H3.3 genes were also highly expressed outside of S phase,
consistent with their status as replication-independent genes. Using a
combination of isotopic labeling and quantitative tandem mass
spectrometry, Hake et al. (2006) showed that the H3.1, H3.2, and H3.3
proteins differed in their posttranslational modifications. H3.1 was
enriched in marks associated with both gene activation and gene
silencing, H3.2 was enriched in repressive marks associated with gene
silencing and the formation of facultative heterochromatin, and H3.3 was
enriched in marks associated with transcriptional activation. Hake et
al. (2006) concluded that H3.1, H3.2, and H3.3 likely have unique
functions and should not be treated as equivalent proteins.

Xu et al. (2010) reported that significant amounts of histone H3.3-H4
tetramers split in vivo, whereas most H3.1-H4 tetramers remain intact
during mitotic division. Inhibiting DNA replication-dependent deposition
greatly reduced the level of splitting events, which suggested that (i)
the replication-independent H3.3 deposition pathway proceeds largely by
cooperatively incorporating 2 new H3.3-H4 dimers, and (ii) the majority
of splitting events occurred during replication-dependent deposition. Xu
et al. (2010) concluded that 'silent' histone modifications within large
heterochromatic regions are maintained by copying modifications from
neighboring preexisting histones without the need for H3-H4 splitting
events.

Talbert and Henikoff (2010) reviewed the assembly of canonical
nucleosomes, which is thought to begin with a tetramer of 2 H3 molecules
and 2 H4 molecules held together by strong bonds between the H3
molecules. H3.1 is the major canonical H3 assembled into chromatin by
the histone chaperone CAF1 (see 601246) complex during DNA replication
and repair. The replacement histone H3.3 is assembled by the histone
regulator A (HIRA; 600237) complex independently of DNA synthesis.

- Methylation and Demethylation of H3 Histones

Eukaryotic genomes are organized into discrete structural and functional
chromatin domains. Noma et al. (2001) demonstrated that distinct
site-specific histone H3 methylation patterns define euchromatic and
heterochromatic chromosomal domains within an 47-kb region of the mating
type locus in fission yeast. H3 methylated at lysine-9 (H3K9), and its
interacting Swi6 protein, are strictly localized to a 20-kb silent
heterochromatic interval. In contrast, H3 methylated at lysine-4 (H3K4)
is specific to the surrounding euchromatic regions. Two inverted repeats
flanking the silent interval serve as boundary elements to mark the
borders between heterochromatin and euchromatin. Deletions of these
boundary elements leads to spreading of H3K9 methylation and Swi6 into
neighboring sequences. Furthermore, the H3K9 methylation and
corresponding heterochromatin-associated complexes prevent H3K4
methylation in the silent domain.

Coating of the X chromosome by XIST (314670) RNA is an essential trigger
for X inactivation. Heard et al. (2001) reported that methylation of
lys9 of histone H3 on the inactive X chromosome occurs immediately after
XIST RNA coating and before transcriptional inactivation of X-linked
genes. X-chromosomal H3-lys9 methylation occurs during the same window
of time as H3-lys9 hypoacetylation and H3-lys4 hypomethylation. Histone
H3 modifications thus represent the earliest known chromatin changes
during X inactivation. The authors also identified a unique 'hotspot' of
H3-lys9 methylation 5-prime to XIST and proposed that this acts as a
nucleation center for XIST RNA-dependent spread of inactivation along
the X chromosome via H3-lys9 methylation.

Boggs et al. (2002) and Peters et al. (2002) showed that methylation of
H3 histone at lys9 occurs in facultative heterochromatin of the inactive
X chromosome in female mammals. Posttranslational modifications of
histone amino termini are an important regulatory mechanism that induce
transitions in chromatin structure, thereby contributing to epigenetic
gene control and the assembly of specialized chromosomal subdomains.
Methylation of histone H3 at lys9 by site-specific histone
methyltransferases marks constitutive heterochromatin. Boggs et al.
(2002) found that, in contrast, H3 methylated at lys4 is depleted in the
inactive X chromosome, except in 3 'hotspots' of enrichment along its
length. They could show that lys9 methylation is associated with
promoters of inactive genes, whereas lys4 methylation is associated with
active genes on the X chromosome. The data demonstrated that
differential methylation at 2 distinct sites of the H3 amino terminus
correlates with contrasting gene activities and may be part of a
'histone code' involved in establishing and maintaining facultative
heterochromatin.

Peters et al. (2002) showed H3-lys9 methylation is retained through
mitosis, indicating that it might provide an epigenetic imprint for the
maintenance of the inactive state. Disruption of the 2 site-specific
histone methyltransferases in the mouse abolished H3-lys9 methylation of
constitutive heterochromatin, but not that of the inactive X chromosome.

In Saccharomyces pombe, Volpe et al. (2002) deleted the argonaute
(606228), dicer (606241), and RNA-dependent RNA polymerase gene
homologs, which encode part of the machinery responsible for RNA
interference. Deletion resulted in the aberrant accumulation of
complementary transcripts from centromeric heterochromatic repeats. This
was accompanied by transcription of derepression of transgenes
integrated at the centromere, loss of histone H3-lys9 methylation, and
impairment of centromere function. Volpe et al. (2002) proposed that
double-stranded RNA arising from centromeric repeats targets formation
and maintenance of heterochromatin through RNA interference.

The higher-order assembly of chromatin imposes structural organization
on the genetic information of eukaryotes and is thought to be largely
determined by posttranslational modification of histone tails. Hall et
al. (2002) studied a 20-kb silent domain at the mating-type region of S.
pombe as a model for heterochromatin formation. They found that although
histone H3 methylated at lys9 directly recruited heterochromatin protein
Swi6/HP1 (604478), the critical determinant for H3-lys9 methylation to
spread in cis to be inherited through mitosis and meiosis is Swi6
itself. The authors demonstrated that a centromere homologous repeat
present at the silent mating-type region is sufficient for
heterochromatin formation at an ectopic site, and that its repressive
capacity is mediated by components of the RNA interference machinery.
Moreover, the centromere homologous repeat and the RNA interference
machinery cooperate to nucleate heterochromatin assembly at the
endogenous mating locus but are dispensable for its subsequent
inheritance. Hall et al. (2002) concluded that their work defines
sequential requirements for the initiation and propagation of regional
heterochromatic domains.

Plath et al. (2003) demonstrated that transient recruitment of the EED
(605984)-EZH2 (601573) complex to the inactive X chromosome occurs
during initiation of X inactivation in both extraembryonic and embryonic
cells and is accompanied by H3 lys27 methylation. Recruitment of the
complex and methylation on the inactive X depend on Xist (314670) RNA
but are independent of its silencing function. Plath et al. (2003)
concluded that taken together, their results suggest a role for
EED-EZH2-mediated H3 lys27 methylation during initiation of both
imprinted and random X inactivation and demonstrate that H3 lys27
methylation is not sufficient for silencing of the inactive X.

Methylation of histone tails has been implicated in long-term epigenetic
memory. Methylated H3K4 is a generally conserved mark for euchromatic,
transcriptionally active regions. Rougeulle et al. (2003) described a
profile of H3K4 dimethylation that was specific for monoallelically
expressed genes. Both X-linked genes subject to X inactivation and
autosomal imprinted genes had dimethylated H3K4 restricted to their
promoter regions. In contrast, high levels of H3K4 dimethylation were
found in both promoters and exonic parts of autosomal genes and of
X-linked genes that escaped X inactivation. Rougeulle et al. (2003)
suggested that this pattern of promoter-restricted H3K4 dimethylation,
already present in totipotent cells, may be causally related to the
long-term programming of allelic expression and may provide an
epigenetic mark for monoallelically expressed genes.

Huyen et al. (2004) found that the tandem tudor domain of 53BP1 (605230)
bound histone H3 methylated on lys79 in vitro. Suppression of DOT1L
(607375), the enzyme that methylates lys79 of histone H3, also inhibited
recruitment of 53BP1 to double-strand breaks. Because methylation of
histone H3 lys79 was unaltered in response to DNA damage, Huyen et al.
(2004) proposed that 53BP1 senses double-strand breaks indirectly
through changes in higher-order chromatin structure that expose the
53BP1 binding site.

Cha et al. (2005) showed that AKT (164730) phosphorylates EZH2 (601573)
at serine-21 and suppresses its methyltransferase activity by impeding
EZH2 binding to histone H3, which results in a decrease of lysine-27
trimethylation and derepression of silenced genes. Cha et al. (2005)
concluded that their results imply that AKT regulates the methylation
activity, through phosphorylation of EZH2, which may contribute to
oncogenesis.

Lee et al. (2005) showed that BHC110 (609132)-containing complexes
showed a near 5-fold increase in demethylation of H3K4 compared to
recombinant BHC110. Furthermore, recombinant BHC110 was unable to
demethylate H3K4 on nucleosomes, but BHC110-containing complexes readily
demethylated nucleosomes. In vitro reconstitution of the BHC complex
using recombinant subunits revealed an essential role for the REST
corepressor CoREST (607675), not only in stimulating demethylation on
core histones but also promoting demethylation of nucleosomal
substrates. Lee et al. (2005) found that nucleosomal demethylation was
the result of CoREST enhancing the association between BHC110 and
nucleosomes. Depletion of CoREST in in vivo cell culture resulted in
derepression of REST-responsive gene expression and increased
methylation of H3K4. Taken together, Lee et al. (2005) concluded that
their results highlight an essential role for CoREST in demethylation of
H3K4 both in vitro and in vivo.

Wysocka et al. (2006) showed that a plant homeodomain (PHD) finger of
nucleosome remodeling factor (NURF), an ISWI-containing ATP-dependent
chromatin-remodeling complex, mediates a direct preferential association
with trimethylated H3K4 tails. Depletion of trimethylated H3K4 causes
partial release of the NURF subunit BPTF (601819) from chromatin and
defective recruitment of the associated ATPase, SNF2L1 (SMARCA1;
300012), to the HOXC8 (142970) promoter. Loss of BPTF in Xenopus embryos
mimics WDR5 (609012) loss-of-function phenotypes, and compromises
spatial control of Hox gene expression. Wysocka et al. (2006) suggested
that WDR5 and NURF function in a common biologic pathway in vivo, and
that NURF-mediated ATP-dependent chromatin remodeling is directly
coupled to H3K4 trimethylation to maintain HOX gene expression patterns
during development.

Shi et al. (2006) identified a novel class of methylated H3K4 effector
domains, the PHD domains of the ING (see 601566) family of tumor
suppressor proteins. The ING PHD domains are specific and highly robust
binding modules for tri- and dimethylated H3K4. ING2 (604215), a native
subunit of a repressive mSin3a (607776)-HDAC1 (601241) histone
deacetylase complex, binds with high affinity to the trimethylated
species. In response to DNA damage, recognition of trimethylated H3K4 by
the ING2 PHD domain stabilizes the mSin3a-HDAC1 complex in promoters of
proliferation genes. In addition, ING2 modulates cellular responses to
genotoxic insults, and these functions are critically dependent on ING2
interaction with trimethylated H3K4. Shi et al. (2006) concluded that
trimethylation of K4 on histone 3 plays a pivotal role in gene
repression and potentially in tumor suppressor mechanisms.

In a search for proteins and complexes interacting with trimethylated
histone H3K9, Cloos et al. (2006) identified JMJD2C (605469). Cloos et
al. (2006) showed that 3 members of the JMJD2 subfamily of proteins
demethylate tri- or dimethylated H3K9 in vitro through a hydroxylation
reaction requiring iron and alpha-ketoglutarate as cofactors. They
demonstrated also that ectopic expression of JMJD2C or other JMJD2
members markedly decreased tri- and dimethylated H3K9 levels, increased
monomethylated H3K9, delocalized HP1 (see 604478), and reduced
heterochromatin in vivo. In agreement with studies indicating a
contribution of JMJD2C to tumor development, inhibition of JMJD2C
expression decreased cell proliferation.

Klose et al. (2006) demonstrated that JMJD2A is capable of removing the
trimethyl group from modified H3K9 and H3K36. Overexpression of JMJD2A
abrogated recruitment of HP1 to heterochromatin, indicating a role for
JMJD2A in antagonizing methylated H3K9 nucleated events. siRNA-mediated
knockdown of JMJD2A led to increased levels of H3K9 methylation and
upregulation of a JMJD2A target gene, ASCL2 (601886), indicating that
JMJD2A may function in euchromatin to remove histone methylation marks
that are associated with active transcription.

Mikkelsen et al. (2007) reported the application of
single-molecule-based sequencing technology for high-throughput
profiling of histone modifications in mammalian cells. By obtaining over
4 billion bases of sequence from chromatin immunoprecipitated DNA, they
generated genomewide chromatin-state maps of mouse embryonic stem cells,
neural progenitor cells, and embryonic fibroblasts. Mikkelsen et al.
(2007) found that H3 lysine-4 and H3 lysine-27 trimethylation
effectively discriminated genes that are expressed, poised for
expression, or stably repressed, and therefore reflected cell state and
lineage potential. H3 lysine-36 trimethylation marks primary coding and
noncoding transcripts, facilitating gene annotation. Trimethylation of
lysine-9 and lysine-20 is detected at satellite, telomeric, and active
long-terminal repeats, and can spread into proximal unique sequences. H3
lysine-4 and lysine-9 trimethylation marks imprinting control regions.
Chromatin state could be read in an allele-specific manner by using
single-nucleotide polymorphisms. Mikkelsen et al. (2007) concluded that
their study provides a framework for the application of comprehensive
chromatin profiling towards characterization of diverse mammalian cell
populations.

Using mass spectrometry, Ooi et al. (2007) identified the main proteins
that interacted in vivo with the product of an epitope-tagged allele of
the endogenous DNMT3L (606588) gene as DNMT3A2 (602769), DNMT3B
(602900), and the 4 core histones. Peptide interaction assays showed
that DNMT3L specifically interacts with the extreme amino terminus of
histone H3; this interaction was strongly inhibited by methylation at
lysine-4 of histone H3 but was insensitive to modifications at other
positions. Crystallographic studies of human DNMT3L showed that the
protein has a carboxy-terminal methyltransferase-like domain and an
N-terminal cysteine-rich domain. Cocrystallization of DNMT3L with the
tail of histone H3 revealed that the tail bound to the cysteine-rich
domain of DNMT3L, and substitution of key residues in the binding site
eliminated the H3 tail-DNMT3L interaction. Ooi et al. (2007) concluded
that DNMT3L recognizes histone H3 tails that are unmethylated at
lysine-4 and induces de novo DNA methylation by recruitment or
activation of DNMT3A2.

Lan et al. (2007) reported that, in contrast to the PHD fingers of the
bromodomain PHD finger transcription factor (BPTF; 601819) and inhibitor
of growth family 2 (ING2; 604215), which bind methylated H3K4, the PHD
finger of BHC80 binds unmethylated H3K4 (H3K4me0), and this interaction
is specifically abrogated by methylation of H3K4. The crystal structure
of the PHD finger of BHC80 bound to an unmodified H3 peptide revealed
the structural basis of the recognition of H3K4me0. Knockdown of BHC80
by RNA inhibition resulted in the derepression of LSD1 target genes, and
this repression was restored by the reintroduction of wildtype BHC80 but
not by a PHD finger mutant that could not bind H3. Chromatin
immunoprecipitation showed that BHC80 and LSD1 depend reciprocally on
one another to associate with chromatin. Lan et al. (2007) concluded
that their findings coupled the function of BHC80 to that of LSD1, and
indicated that unmodified H3K4 is part of the histone code. The authors
further raised the possibility that the generation and recognition of
the unmodified state on histone tails in general might be just as
crucial as posttranslational modifications of histone for chromatin and
transcriptional regulation.

Lee et al. (2007) showed that human UTX (300128), a member of the
Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase.
UTX occupies the promoters of HOX gene clusters (see 142950) and
regulates their transcriptional output by modulating the recruitment of
polycomb repressive complex 1 (PRC1) and the monoubiquitination of
histone H2A (see 602786). Moreover, UTX associates with mixed-lineage
leukemia (MLL) 2/3 complexes (602113, 606833, respectively), and during
retinoic acid signaling events, the recruitment of the UTX complex to
HOX genes results in H3K27 demethylation and a concomitant methylation
of H3K4. Lee et al. (2007) concluded that their results suggested a
concerted mechanism for transcriptional activation in which cycles of
H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27
through UTX.

The arginine at position 2 of histone H3 (H3R2) is asymmetrically
dimethylated (H3R2me2a) in mammalian cells (Torres-Padilla et al.,
2007). Kirmizis et al. (2007) demonstrated that H3R2 is also methylated
in S. cerevisiae, and by using an antibody specific for H3R2me2a in a
chromatin immunoprecipitation (ChIP)-on-chip analysis, they determined
the distribution of this modification on the entire yeast genome. They
found that H3R2me2A is enriched throughout all heterochromatic loci and
inactive euchromatic genes and is present at the 3-prime end of
moderately transcribed genes. In all cases the pattern of H3R2
methylation is mutually exclusive with the trimethyl form of H3K4
(H3K4me3). Kirmizis et al. (2007) showed that methylation at H3R2
abrogates the trimethylation of H3K4 by the Set1 methyltransferase (see
611052). The specific effect on H3K4me3 results from the occlusion of
Spp1, a Set1 methyltransferase subunit necessary for trimethylation.
Kirmizis et al. (2007) concluded that the inability of Spp1 to recognize
H3 methylated at R2 prevents Set1 from trimethylating H3K4. Kirmizis et
al. (2007) stated that their results provided the first mechanistic
insight into the function of arginine methylation on chromatin.

Following up on the observation that asymmetric dimethylation of histone
H3R2 (H3R2me2a) countercorrelates with di- and trimethylation of H3K4
(H3K4me2, H3K4me3) on human promoters, Guccione et al. (2007)
demonstrated that the arginine methyltransferase PRMT6 (608274)
catalyzes H3R2 dimethylation in vitro and controls global levels of
H3R2me2a in vivo. H3R2 methylation by PRMT6 was prevented by the
presence of H3K4me3 on the H3 tail. Conversely, the H3R2me2a mark
prevented methylation of H3K4 as well as binding to the H3 tail by an
ASH2 (604782)/WDR5 (609012)/MLL (159555) family methyltransferase
complex. Chromatin immunoprecipitation showed that H3R2me2a was
distributed within the body and at the 3-prime end of human genes,
regardless of their transcriptional state, whereas it was selectively
and locally depleted from active promoters, coincident with the presence
of H3K4me3. Guccione et al. (2007) concluded that hence, the mutual
antagonism between H3R2 and H3K4 methylation, together with the
association of MLL family complexes with the basal transcription
machinery, may contribute to the localized patterns of H3K4
trimethylation characteristic of transcriptionally poised or active
promoters in mammalian genomes.

Perillo et al. (2008) analyzed how H3 histone methylation and
demethylation control expression of estrogen-responsive genes and showed
that a DNA-bound estrogen receptor (see ESRA, 133430) directs
transcription by participating in bending chromatin to contact the RNA
polymerase II (see 180660) recruited to the promoter. This process is
driven by receptor-targeted demethylation of H3K9 at both enhancer and
promoter sites and is achieved by activation of resident LSD1 (609132)
demethylase. Localized demethylation produces hydrogen peroxide, which
modifies the surrounding DNA and recruits 8-oxoguanine-DNA glycosylase 1
(601982) and topoisomerase II-beta (126431), triggering chromatin and
DNA conformational changes that are essential for estrogen-induced
transcription. Perillo et al. (2008) concluded that their data showed a
strategy that uses controlled DNA damage and repair to guide productive
transcription.

Using high-resolution SNP genotyping to identify regions of genomic gain
and loss in 212 medulloblastoma tumors (155255), Northcott et al. (2009)
identified several focal genetic events in genes targeting histone
methylation at lysine residues, particularly that of H3K9. In vitro
studies showed that restoring expression of genes controlling H3K9
methylation greatly diminished proliferation of medulloblastoma cells.
Northcott et al. (2009) postulated that defective control of the histone
code may contribute to the pathogenesis of medulloblastoma.

Ciccone et al. (2009) demonstrated that KDM1B (613081) functions as a
H3K4 demethylase and is required for de novo DNA methylation of some
imprinted genes in oocytes. KDM1B is highly expressed in growing oocytes
where genomic imprints are established. Targeted disruption of the gene
encoding KDM1B had no effect on mouse development or oogenesis. However,
oocytes from KDM1B-deficient females showed a substantial increase in
H3K4 methylation and failed to set up the DNA methylation marks at 4 out
of 7 imprinted genes examined. Embryos derived from these oocytes showed
biallelic expression or biallelic suppression of the affected genes and
died before midgestation. Ciccone et al. (2009) concluded that
demethylation of H3K4 is critical for establishing the DNA methylation
imprints during oogenesis.

Nucleosomes are largely replaced by protamine in mature human sperm.
Hammoud et al. (2009) showed that the retained nucleosomes were
significantly enriched at loci of developmental importance, including
imprinted gene clusters, microRNA clusters, HOX gene clusters, and
promoters of stand-alone developmental transcription and signaling
factors. Histone modifications localized to particular developmental
loci. H3K4me2 was enriched at certain developmental promoters, whereas
large blocks of H3K4me3 localized to a subset of developmental
promoters, regions in HOX clusters, certain noncoding RNAs, and
generally to paternally expressed imprinted loci, but not paternally
repressed loci. H3K27me3 was significantly enriched at developmental
promoters that were repressed in early embryos, including many bivalent
promoters (i.e., bearing both H3K4me3 and H3K27me3) in embryonic stem
cells. Developmental promoters were generally DNA hypomethylated in
sperm, but they acquired methylation during differentiation. Hammoud et
al. (2009) concluded that epigenetic marking in sperm is extensive and
is correlated with developmental regulators.

Maze et al. (2010) identified an essential role for H3K9 dimethylation
and the lysine dimethyltransferase G9a (604599) in cocaine-induced
structural and behavioral plasticity in mouse. Repeated cocaine
administration reduced global levels of H3K9 dimethylation in the
nucleus accumbens. This reduction in histone methylation was mediated
through the repression of G9a in this brain region, which was regulated
by the cocaine-induced transcription factor delta-FosB (164772). Using
conditional mutagenesis and viral-mediated gene transfer, Maze et al.
(2010) found that G9a downregulation increased the dendritic spine
plasticity of nucleus accumbens neurons and enhanced the preference for
cocaine, thereby establishing a crucial role for histone methylation in
the long-term actions of cocaine.

Luco et al. (2010) demonstrated a direct role for histone modifications,
specifically, trimethylation of H3 at lys36 (H3-K36me3), in alternative
splicing. The authors found that MRG15 (607303) distribution along the
polypyrimidine tract-binding protein (PTB; 600693)-dependent
alternatively spliced genes FGFR2 (176943), TPM2 (190990), TPM1
(191010), and PKM2 (179050), but not along the control gene CD44
(107269), mimicked H3-K36me3 distribution. Overexpression of MRG15 was
sufficient to force exclusion of the PTB-dependent exons but did not
significantly alter the inclusion levels of CD44 exon v6. Additional
experiments led Luco et al. (2010) to conclude that the
chromatin-binding protein MRG15 is a modulator of PTB-dependent
alternative splice site selection. The results of Luco et al. (2010) led
them to propose the existence of an adaptor system for the reading of
histone marks by the pre-mRNA splicing machinery. The adaptor system
consists of histone modifications, a chromatin-binding protein that
reads the histone marks, and an interacting splicing regulator. Luco et
al. (2010) concluded that for a subset of PTB-dependent genes, the
adaptor system consists of H3-K36me3, its binding protein MRG15, and the
splicing regulator PTBP1.

He et al. (2010) performed genomewide mapping of nucleosomes marked with
H3K4me2 in upstream AR-binding enhancers in LNCaP prostate cancer cells
before and following stimulation by dihydrotestosterone (DHT). They
found 3 nucleosomes containing H3K4me2 associated with AR-binding sites
in the absence of DHT, including 2 stable flanking nucleosomes
positioned about 200 bp apart, and a labile central nucleosome that
occluded the actual AR-binding site. Following stimulation, H3K4me2 was
detected only in the 2 flanking sites. The central occluding nucleosome
had a higher A/T content than the flanking nucleosomes, and its histone
octamer was more likely to contain the H2A.Z variant. He et al. (2010)
concluded that apparent differences in nucleosome stability may result
from the combination of DNA sequence, histone octamer composition, and
transcription factor binding.

The histone methylase SUV39H1 (300254) participates in the
trimethylation of histone H3 on lysine-9 (H3K9me3), a modification that
provides binding sites for heterochromatin protein 1-alpha (HP1-alpha;
604478) and promotes transcriptional silencing. This pathway was
initially associated with heterochromatin formation and maintenance but
can also contribute to the regulation of euchromatic genes. Allan et al.
(2012) proposed that the SUV39H1-H3K9me3-HP1-alpha pathway participates
in maintaining the silencing of TH1 loci, ensuring TH2 lineage
stability. In TH2 cells that are deficient in SUV39H1, the ratio between
trimethylated and acetylated H3K9 is impaired, and the binding of
HP1-alpha at the promoters of silenced TH1 genes is reduced. Despite
showing normal differentiation, both SUV39H1-deficient TH2 cells and
HP1-alpha-deficient TH2 cells, in contrast to wildtype cells, expressed
TH1 genes when recultured under conditions that drive differentiation
into TH1 cells. In a mouse model of TH2-driven allergic asthma, the
chemical inhibition or loss of SUV39H1 skewed T-cell responses towards
TH1 responses and decreased the lung pathology.

Yuan et al. (2012) reported that polycomb repressive complex-2 (PRC2)
activity is regulated by the density of its substrate nucleosome arrays.
Neighboring nucleosomes activate the PRC2 complex with a fragment of
their H3 histones (ala31 to arg42). Yuan et al. (2012) also identified
mutations on PRC2 subunit Suz12 (606245) that impair its binding and
response to the activating peptide and its ability in establishing H3K27
trimethylation levels in vivo. In mouse embryonic stem cells, local
chromatin compaction occurs before the formation of trimethylated H3K27
upon transcription cessation of the retinoic acid-regulated gene CYP26A1
(602239). Yuan et al. (2012) proposed that PRC2 can sense the chromatin
environment to exert its role in the maintenance of transcriptional
states.

- Phosphorylation and Dephosphorylation of H3 Histones

During the immediate-early response of mammalian cells to mitogens,
histone H3 is rapidly and transiently phosphorylated by 1 or more
kinases. Sassone-Corsi et al. (1999) demonstrated that RSK2 (300075), a
member of the pp90(RSK) family of kinases implicated in growth control,
was required for epidermal growth factor (EGF; 131530)-stimulated
phosphorylation of H3. H3 appears to be a direct or indirect target of
RSK2, suggesting to Sassone-Corsi et al. (1999) that chromatin
remodeling might contribute to mitogen-activated protein
kinase-regulated gene expression.

Anest et al. (2003) demonstrated nuclear accumulation of IKK-alpha
(IKKA; 600664) after cytokine exposure, suggesting a nuclear function
for this protein. Consistent with this, chromatin immunoprecipitation
assays revealed that IKKA was recruited to the promoter regions of
NF-kappa-B (164011)-regulated genes on stimulation with tumor necrosis
factor-alpha (191160). Notably, NF-kappa-B-regulated gene expression was
suppressed by the loss of IKKA, and this correlated with a complete loss
of gene-specific phosphorylation of histone H3 on serine-10, a
modification previously associated with positive gene expression.
Furthermore, Anest et al. (2003) showed that IKKA can directly
phosphorylate histone H3 in vitro, suggesting a new substrate for this
kinase. Anest et al. (2003) proposed that IKKA is an essential regulator
of NFKB-dependent gene expression through control of promoter-associated
histone phosphorylation after cytokine exposure.

Yamamoto et al. (2003) independently demonstrated that IKKA functions in
the nucleus to activate the expression of NF-kappa-B-responsive genes
after stimulation with cytokines. IKKA interactions with CREB-binding
protein (600140) and in conjunction with RELA (164014) is recruited to
NF-kappa-B-responsive promoters and mediates the cytokine-induced
phosphorylation and subsequent acetylation of specific residues in
histone H3. Yamamoto et al. (2003) concluded that their results define a
new nuclear role of IKKA in modifying histone function that is critical
for the activation of NF-kappa-B-directed gene expression.

Fischle et al. (2005) demonstrated that HP1-alpha (604478), HP1-beta
(604511), and HP1-gamma (604477) are released from chromatin during the
M phase of the cell cycle, even though trimethylation levels of H3K9
remain unchanged. However, the additional transient modification of
histone H3 by phosphorylation of ser10 next to the more stable
methyl-lys9 mark is sufficient to eject HP1 proteins from their binding
sites. Inhibition or depletion of the mitotic kinase Aurora B (604970),
which phosphorylates histone H3 on ser10, causes retention of HP1
proteins on mitotic chromosomes, suggesting that H3 ser10
phosphorylation is necessary for the dissociation of HP1 from chromatin
in M phase. Fischle et al. (2005) concluded that their findings
establish a regulatory mechanism of protein-protein interactions,
through a combinatorial readout of 2 adjacent posttranslational
modifications: a stable methylation and a dynamic phosphorylation mark.

Dawson et al. (2009) showed that human JAK2 (147796) is present in the
nucleus of hematopoietic cells and directly phosphorylates tyr41 (Y41)
on histone H3. Heterochromatin protein 1-alpha (HP1-alpha, 604478), but
not HP1-beta (604511), specifically binds to this region of H3 through
its chromo-shadow domain. Phosphorylation of H3Y41 by JAK2 prevents this
binding. Inhibition of JAK2 activity in human leukemic cells decreases
both the expression of hematopoietic oncogene LMO2 (180385) and the
phosphorylation of H3Y41 at its promoter, while simultaneously
increasing the binding of HP1-alpha at the same site. Dawson et al.
(2009) concluded that their results identified a previously unrecognized
nuclear role for JAK2 in the phosphorylation of H3Y41 and revealed a
direct mechanistic link between 2 genes, JAK2 and LMO2, involved in
normal hematopoiesis and leukemia.

Metzger et al. (2010) demonstrated that phosphorylation of histone H3 at
threonine-6 (H3T6) by protein kinase C (PKC)-beta-1 (176970) is the key
event that prevents LSD1 (609132) from demethylating H3K4 during
androgen receptor (AR; 313700)-dependent gene activation. In vitro,
histone H3 peptides methylated at lysine-4 and phosphorylated at
threonine-6 were no longer LSD1 substrates. In vivo, PKC-beta-1
colocalized with AR and LSD1 on target gene promoters and phosphorylated
H3T6 after androgen-induced gene expression. RNAi-mediated knockdown of
PKC-beta-1 abrogated H3T6 phosphorylation, enhanced demethylation at
H3K4, and inhibited AR-dependent transcription. Activation of PKCB1
requires androgen-dependent recruitment of the gatekeeper kinase protein
kinase C-related kinase 1 (PRK1; 601032). Notably, increased levels of
PKCB1 and phosphorylated H3T6 (H3T6ph) positively correlated with high
Gleason scores of prostate carcinomas, and inhibition of PKC-beta-1
blocked AR-induced tumor cell proliferation in vitro and cancer
progression of tumor xenografts in vivo. Together, Metzger et al. (2010)
concluded that androgen-dependent kinase signaling leads to the writing
of the new chromatin mark H3T6ph, which in consequence prevents removal
of active methyl marks from H3K4 during AR-stimulated gene expression.

Wang et al. (2010) showed that phosphorylation of histone H3 threonine-3
(H3T3) by haspin (609240) is necessary for chromosomal passenger complex
(CPC) accumulation at centromeres and that the CPC subunit survivin
(603352) binds directly to phosphorylated H3T3 (H3T3ph). A nonbinding
survivin-D70A/D71A mutant did not support centromeric CPC concentration,
and both haspin depletion and survivin-D70A/D71A mutation diminished
centromere localization of the kinesin MCAK (604538) and the mitotic
checkpoint response to taxol. Survivin-D70A/D71A mutation and
microinjection of H3T3ph-specific antibody both compromised centromeric
Aurora B (604970) functions but did not prevent cytokinesis. Therefore,
Wang et al. (2010) concluded that H3T3ph generated by haspin positions
the chromosomal passenger complex at centromeres to regulate selected
targets of Aurora B during mitosis.

Kelly et al. (2010) demonstrated that H3T3ph is directly recognized by
an evolutionarily conserved binding pocket in the BIR domain of the CPC
subunit survivin. This binding mediates recruitment of the CPC to
chromosomes and the resulting activation of its kinase subunit Aurora B.
Consistently, modulation of the kinase activity of haspin, which
phosphorylates H3T3, leads to defects in the Aurora B-dependent
processes of spindle assembly and inhibition of nuclear reformation.
Kelly et al. (2010) concluded that their findings established a direct
cellular role for mitotic H3T3 phosphorylation, which is read and
translated by the CPC to ensure accurate cell division.

Yamagishi et al. (2010) showed that phosphorylation of H3T3 mediated by
haspin cooperates with bub1 (602452)-mediated histone 2A-serine-121
(H2A-S121) phosphorylation in targeting the CPC to the inner centromere
in fission yeast and human cells. Phosphorylated H3T3 promotes
nucleosome binding of survivin, whereas phosphorylated H2A-S121
facilitates the binding of shugoshin (609168), the centromeric CPC
adaptor. Haspin colocalizes with cohesin by associating with Pds5 (see
613200), whereas bub1 localizes at kinetochores. Thus, Yamagishi et al.
(2010) concluded that the inner centromere is defined by intersection of
2 histone kinases.

Healy et al. (2012) reviewed the role of phosphorylation of H3 at ser10
and ser28 by MSK1 (RPS6KA5; 603607)/MSK2 (RPS6KA4; 603606) in the
regulation of immediate-early genes, such as JUN (165160) and FOS
(164810).

- Acetylation and Deacetylation of H3 Histones

Agalioti et al. (2002) found that only a small subset of lysines in
histones H3 and H4 are acetylated in vivo by the GCN5 acetyltransferase
(see 602301) during activation of the interferon-beta gene (IFNB;
147640). Reconstitution of recombinant nucleosomes bearing mutations in
these lysine residues revealed the cascade of gene activation via a
point-by-point interpretation of the histone code through the ordered
recruitment of bromodomain-containing transcription complexes.
Acetylation of histone H4 lys8 mediates recruitment of the SWI/SNF
complex (see 603111), whereas acetylation of lys9 and lys14 in histone
H3 is critical for the recruitment of TFIID (see 313650). Thus, the
information contained in the DNA address of the enhancer is transferred
to the histone N termini by generating novel adhesive surfaces required
for the recruitment of transcription complexes.

Masumoto et al. (2005) showed that acetylation of the lysine at position
56 (K56) in histone H3 is an abundant modification of newly synthesized
histone H3 molecules that are incorporated into chromosomes during S
phase. Defects in the acetylation of K56 in histone H3 result in
sensitivity to genotoxic agents that cause DNA strand breaks during
replication. In the absence of DNA damage, the acetylation of K56
largely disappears in G2. In contrast, cells with DNA breaks maintain
high levels of acetylation, and the persistence of the modification is
dependent on DNA damage checkpoint proteins. Masumoto et al. (2005)
suggested that the acetylation of histone H3 K56 in S. cerevisiae
creates a favorable chromatin environment for DNA repair and that a key
component of the DNA damage response is to preserve this acetylation.

Michishita et al. (2008) showed that the human SIRT6 protein (606211) is
an NAD(+)-dependent histone H3K9 deacetylase that modulates telomeric
chromatin. They showed that SIRT6 associates specifically with
telomeres, and SIRT6 depletion led to telomere dysfunction with
end-to-end chromosomal fusions and premature cellular senescence.
Moreover, SIRT6-depleted cells exhibited abnormal telomere structures
that resemble defects observed in Werner syndrome (277700), a premature
aging disorder. At telomeric chromatin, SIRT6 deacetylated H3K9 and was
required for the stable association of RECQL2 (604611), the factor that
is mutated in Werner syndrome. Michishita et al. (2008) proposed that
SIRT6 contributes to the propagation of a specialized chromatin state at
mammalian telomeres, which in turn is required for proper telomere
metabolism and function. The authors concluded that their findings
constituted the first identification of a physiologic enzymatic activity
of SIRT6, and linked chromatin regulation by SIRT6 to telomere
maintenance and to a human premature aging syndrome.

Das et al. (2009) demonstrated that the histone acetyltransferase CBP
(600140) in flies, and CBP and p300 (602700) in humans, acetylate H3K56,
whereas Drosophila sir2 and human SIRT1 (604479) and SIRT2 (604480)
deacetylate H3K56 acetylation. The histone chaperones ASF1A (609189) in
humans and Asf1 in Drosophila are required for acetylation of H3K56 in
vivo, whereas the histone chaperone CAF1 (see 601245) in humans and Caf1
in Drosophila are required for the incorporation of histones bearing
this mark into chromatin. Das et al. (2009) showed that, in response to
DNA damage, histones bearing acetylated K56 are assembled into chromatin
in Drosophila and human cells, forming foci that colocalize with sites
of DNA repair. Furthermore, acetylation of H3K56 is increased in
multiple types of cancer, correlating with increased levels of ASF1A in
these tumors. Das et al. (2009) concluded that their identification of
multiple proteins regulating the levels of H3K56 acetylation in
metazoans will allow future studies of this critical and unique histone
modification that couples chromatin assembly to DNA synthesis, cell
proliferation, and cancer.

MOLECULAR GENETICS

Zaidi et al. (2013) compared the incidence of de novo mutations in 362
severe congenital heart disease cases and 264 controls by analyzing
exome sequencing of parent-offspring trios. Congenital heart disease
cases showed a significant excess of protein-altering de novo mutations
in genes expressed in the developing heart, with an odds ratio of 7.5
for damaging (premature termination, frameshift, splice site) mutations.
Similar odds ratios were seen across the main classes of severe
congenital heart disease. Zaidi et al. (2013) found a marked excess of
de novo mutations in genes involved in the production, removal, or
reading of histone 3 lysine-4 (H3K4) methylation or ubiquitination of
H2BK120 (see 609904), which is required for H3K4 methylation. There were
also 2 de novo mutations in SMAD2 (601366), which regulates H3K27
methylation in the embryonic left right organizer. The combination of
both activating (H3K4 methylation) and inactivating (H3K27 methylation)
chromatin marks characterizes 'poised' promoters and enhancers, which
regulate expression of key developmental genes.

BIOCHEMICAL FEATURES

As revealed by the structure of the chromodomain of HP1 (see 604511)
bound to a histone H3 peptide dimethylated at N-zeta of lys9, Nielsen et
al. (2002) showed that HP1 uses an induced-fit mechanism to recognize
the methylation of lys9. The side chain of lys9 is almost fully extended
and surrounded by residues that are conserved in many other
chromodomains. The QTAR peptide sequence preceding lys9 performs most of
the additional interactions with the chromodomain, with HP1 residues
val23, leu40, trp42, leu58, and cys60 appearing to be a major
determinant of specificity by binding the key buried ala7. Nielsen et
al. (2002) concluded that their findings predict which other
chromodomains will bind methylated proteins and suggest a motif that
they might recognize.

Using deuterium exchange/mass spectrometry coupled with hydrodynamic
measures, Black et al. (2004) demonstrated that CENPA (117139) and
histone H4 form subnucleosomal tetramers that are more compact and
conformationally more rigid than the corresponding tetramers of histones
H3 and H4. Substitution into histone H3 of the domain of CENPA
responsible for compaction was sufficient to direct it to centromeres.
Thus, Black et al. (2004) concluded that the centromere-targeting domain
of CENPA confers a unique structural rigidity to the nucleosomes into
which it assembles, and is likely to have a role in maintaining
centromere identity.

NOMENCLATURE

Marzluff et al. (2002) provided a nomenclature for replication-dependent
histone genes located within the HIST1, HIST2, and HIST3 clusters. The
symbols for these genes all begin with HIST1, HIST2, or HIST3 according
to which cluster they are located in. The H2A, H2B, H3, and H4 genes
were named systematically according to their location within the HIST1,
HIST2, and HIST3 clusters. For example, HIST1H3A is the most telomeric
H3 gene within HIST1, and HIST1H3J (602817) is the most centromeric. In
contrast, the H1 genes, all of which are located within HIST1, were
named according to their mouse homologs. Thus, HIST1H1A (142709) is
homologous to mouse H1a, HIST1H1B (142711) is homologous to mouse H1b,
and so on.

*FIELD* RF
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3. Allan, R. S.; Zueva, E.; Cammas, F.; Schreiber, H. A.; Masson,
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8. Ciccone, D. N.; Su, H.; Hevi, S.; Gay, F.; Lei, H.; Bajko, J.;
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10. Das, C.; Lucia, M. S.; Hansen, K. C.; Tyler, J. K.: CBP/p300-mediated
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25. Lee, M. G.; Villa, R.; Trojer, P.; Norman, J.; Yan, K.-P.; Reinberg,
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26. Lee, M. G.; Wynder, C.; Cooch, N.; Shiekhattar, R.: An essential
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27. Luco, R. F.; Pan, Q.; Tominaga, K.; Blencowe, B. J.; Pereira-Smith,
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28. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais,
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29. Masumoto, H.; Hawke, D.; Kobayashi, R.; Verreault, A.: A role
for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA
damage response. Nature 436: 294-298, 2005.

30. Maze, I.; Covington, H. E., III; Dietz, D. M.; LaPlant, Q.; Renthal,
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A.; Schaefer, A.; Nestler, E. J.: Essential role of the histone methyltransferase
G9a in cocaine-induced plasticity. Science 327: 213-216, 2010.

31. Metzger, E.; Imhof, A.; Patel, D.; Kahl, P.; Hoffmeyer, K.; Friedrichs,
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Beisenherz-Huss, C.; Gunther, T.; Buettner, R.; Schule, R.: Phosphorylation
of histone H3T6 by PKC-beta-1 controls demethylation at histone H3K4. Nature 4
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32. Michishita, E.; McCord, R. A.; Berber, E.; Kioi, M.; Padilla-Nash,
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J. C.; Chang, H. Y.; Bohr, V. A.; Ried, T.; Gozani, O.; Chua, K. F.
: SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric
chromatin. Nature 452: 492-496, 2008.

33. Mikkelsen, T. S.; Ku, M.; Jaffe, D. B.; Issac, B.; Lieberman,
E.; Giannoukos, G.; Alvarez, P.; Brockman, W.; Kim, T.-K.; Koche,
R. P.; Lee, W.; Mendenhall, E.; and 10 others: Genome-wide maps
of chromatin state in pluripotent and lineage-committed cells. Nature 448:
553-560, 2007.

34. Nielsen, P. R.; Nietilspach, D.; Mott, H. R.; Callaghan, J.; Bannister,
A.; Kouzarides, T.; Murzin, A. G.; Murzina, N. V.; Laue, E. D.: Structure
of the Hp1 chromodomain bound to histone H3 methylated at lysine 9. Nature 416:
103-107, 2002.

35. Noma, K.; Allis, C. D.; Grewal, S. I. S.: Transitions in distinct
histone H3 methylation patterns at the heterochromatin domain boundaries. Scien
ce 293: 1150-1155, 2001.

36. Northcott, P. A.; Nakahara, Y.; Wu, X.; Feuk, L.; Ellison, D.
W.; Croul, S.; Mack, S.; Kongkham, P. N.; Peacock, J.; Dubuc, A.;
Ra, Y.-S.; Zilberberg, K.; and 17 others: Multiple recurrent genetic
events converge on control of histone lysine methylation in medulloblastoma. Na
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37. Ooi, S. K. T.; Qiu, C.; Bernstein, E.; Li, K.; Jia, D.; Yang,
Z.; Erdjument-Bromage, H.; Tempst, P.; Lin, S.-P.; Allis, C. D.; Cheng,
X.; Bestor, T. H.: DNMT3L connects unmethylated lysine 4 of histone
H3 to de novo methylation of DNA. Nature 448: 714-717, 2007.

38. Perillo, B.; Ombra, M. N.; Bertoni, A.; Cuozzo, C.; Sacchetti,
S.; Sasso, A.; Chiariotti, L.; Malorni, A.; Abbondanza, C.; Avvedimento,
E. V.: DNA oxidation as triggered by H3K9me2 demethylation drives
estrogen-induced gene expression. Science 319: 202-206, 2008.

39. Peters, A. H. F. M.; Mermoud, J. E.; O'Carroll, D.; Pagani, M.;
Schweizer, D.; Brockdorff, N.; Jenuwein, T.: Histone H3 lysine 9
methylation is an epigenetic imprint of facultative heterochromatin. Nature
Genet. 30: 77-80, 2002.

40. Plath, K.; Fang, J.; Mlynarczyk-Evans, S. K.; Cao, R.; Worringer,
K. A.; Wang, H.; de la Cruz, C. C.; Otte, A. P.; Panning, B.; Zhang,
Y.: Role of histone H3 lysine 27 methylation in X inactivation. Science 300:
131-135, 2003.

41. Rougeulle, C.; Navarro, P.; Avner, P.: Promoter-restricted H3
Lys 4 di-methylation is an epigenetic mark for monoallelic expression. Hum.
Molec. Genet. 12: 3343-3348, 2003.

42. Sassone-Corsi, P.; Mizzen, C. A.; Cheung, P.; Crosjo, C.; Monaco,
L.; Jacquot, S.; Hanauer, A.; Allis, C. D.: Requirement of Rsk-2
for epidermal growth factor-activated phosphorylation of histone H3. Science 2
85: 886-891, 1999.

43. Shi, X.; Hong, T.; Walter, K. L.; Ewalt, M.; Michishita, E.; Hung,
T.; Carney, D.; Pena, P.; Lan, F.; Kaadige, M. R.; Lacoste, N.; Cayrou,
C.; and 9 others: ING2 PHD domain links histone H3 lysine 4 methylation
to active gene repression. Nature 442: 96-99, 2006.

44. Talbert, P. B.; Henikoff, S.: Histone variants--ancient wrap
artists of the epigenome. Nature Rev. Molec. Cell Biol. 11: 264-275,
2010.

45. Torres-Padilla, M. E.; Parfitt, D. E.; Kouzarides, T.; Zernicka-Goetz,
M.: Histone arginine methylation regulates pluripotency in the early
mouse embryo. Nature 445: 214-218, 2007.

46. Volpe, T. A.; Kidner, C.; Hall, I. M.; Teng, G.; Grewal, S. I.
S.; Martienssen, R. A.: Regulation of heterochromatic silencing and
histone H3 lysine-9 methylation by RNAi. Science 297: 1833-1837,
2002.

47. Wang, F.; Dai, J.; Daum, J. R.; Niedzialkowska, E.; Banerjee,
B.; Stukenberg, P. T.; Gorbsky, G. J.; Higgins, J. M. G.: Histone
H3 Thr-3 phosphorylation by haspin positions Aurora B at centromeres
in mitosis. Science 330: 231-235, 2010.

48. Wysocka, J.; Swigut, T.; Xiao, H.; Milne, T. A.; Kwon, S. Y.;
Landry, J.; Kauer, M.; Tackett, A. J.; Chait, B. T.; Badenhorst, P.;
Wu, C.; Allis, C. D.: A PHD finger of NURF couples histone H3 lysine
4 trimethylation with chromatin remodelling. Nature 442: 86-90,
2006.

49. Xu, M.; Long, C.; Chen, X.; Huang, C.; Chen, S.; Zhu, B.: Partitioning
of histone H3-H4 tetramers during DNA replication-dependent chromatin
assembly. Science 328: 94-98, 2010.

50. Yamagishi, Y.; Honda, T.; Tanno, Y.; Watanabe, Y.: Two histone
marks establish the inner centromere and chromosome bi-orientation. Science 330:
239-233, 2010.

51. Yamamoto, Y.; Verma, U. N.; Prajapati, S.; Kwak, Y.-T.; Gaynor,
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gene expression. Nature 423: 655-659, 2003.

52. Yuan, W.; Wu, T.; Fu, H.; Dai, C.; Wu, H.; Liu, N.; Li, X.; Xu,
M.; Zhang, Z.; Niu, T.; Han, Z.; Chai, J.; Zhou, X. J.; Gao, S.; Zhu,
B.: Dense chromatin activates polycomb repressive complex 2 to regulate
H3 lysine 27 methylation. Science 337: 971-975, 2012.

53. Zaidi, S.; Choi, M.; Wakimoto, H.; Ma, L.; Jiang, J.; Overton,
J. D.; Romano-Adesman, A.; Bjornson, R. D.; Breitbart, R. E.; Brown,
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in histone-modifying genes in congenital heart disease. Nature 498:
220-223, 2013.

*FIELD* CN
Ada Hamosh - updated: 07/24/2013
Patricia A. Hartz - updated: 2/6/2013
Matthew B. Gross - updated: 2/4/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
alopez: 07/24/2013
mgross: 2/6/2013
mgross: 2/4/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/9/1998

MIM 602811
*RECORD*
*FIELD* NO
602811
*FIELD* TI
*602811 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER D; HIST1H3D
;;HISTONE GENE CLUSTER 1, H3D;;
read moreHIST1 CLUSTER, H3D;;
H3 HISTONE FAMILY, MEMBER B; H3FB;;
H3/B
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3D genes. They noted that all H3 genes in histone
gene cluster-1 (HIST1), including HIST1H3D, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes that included H3/B.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3D.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

*FIELD* RF
1. Albig, W.; Kioschis, P.; Poustka, A.; Meergans, K.; Doenecke, D.
: Human histone gene organization: nonregular arrangement within a
large cluster. Genomics 40: 314-322, 1997.

2. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

*FIELD* CN
Matthew B. Gross - updated: 02/04/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
mgross: 02/04/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/9/1998

MIM 602812
*RECORD*
*FIELD* NO
602812
*FIELD* TI
*602812 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER C; HIST1H3C
;;HISTONE GENE CLUSTER 1, H3C;;
read moreHIST1 CLUSTER, H3C;;
H3 HISTONE FAMILY, MEMBER C; H3FC;;
H3/C
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

Kardalinou et al. (1993) identified a gene encoding a member of the H3
class of histones and designated it H3.1. Albig and Doenecke (1997)
designated this gene H3/c.

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3C genes. They noted that all H3 genes in histone
gene cluster-1 (HIST1), including HIST1H3C, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig, Albig et al. (1997) mapped the H3/c gene to
chromosome 6p21.3, within a cluster of 35 histone genes.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3C.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

*FIELD* RF
1. Albig, W.; Doenecke, D.: The human histone gene cluster at the
D6S105 locus. Hum. Genet. 101: 284-294, 1997.

2. Albig, W.; Kioschis, P.; Poustka, A.; Meergans, K.; Doenecke, D.
: Human histone gene organization: nonregular arrangement within a
large cluster. Genomics 40: 314-322, 1997.

3. Kardalinou, E.; Eick, S.; Albig, W.; Doenecke, D.: Association
of a human H1 histone gene with an H2A pseudogene and genes encoding
H2B.1 and H3.1 histones. J. Cell. Biochem. 52: 375-383, 1993.

4. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

*FIELD* CN
Matthew B. Gross - updated: 2/1/2013
Ada Hamosh - updated: 4/13/2010
Ada Hamosh - updated: 10/4/2004
Stylianos E. Antonarakis - updated: 11/26/2002
Ada Hamosh - updated: 2/26/2002
Stylianos E. Antonarakis - updated: 1/7/2002
Victor A. McKusick - updated: 12/11/2001

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
mgross: 02/04/2013
mgross: 2/1/2013
mgross: 7/22/2010
alopez: 4/14/2010
terry: 4/13/2010
wwang: 4/27/2009
carol: 8/15/2006
terry: 8/11/2006
alopez: 10/26/2005
terry: 10/25/2005
alopez: 10/4/2004
tkritzer: 3/31/2003
mgross: 11/26/2002
alopez: 3/12/2002
alopez: 3/1/2002
terry: 2/26/2002
mgross: 1/7/2002
alopez: 1/3/2002
alopez: 12/12/2001
terry: 12/11/2001
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/9/1998

MIM 602813
*RECORD*
*FIELD* NO
602813
*FIELD* TI
*602813 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER E; HIST1H3E
;;HISTONE GENE CLUSTER 1, H3E;;
read moreHIST1 CLUSTER, H3E;;
H3 HISTONE FAMILY, MEMBER D; H3FD;;
H3/D
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

Albig et al. (1991) identified a gene encoding a member of the H3 class
of histones and designated it H3.1. Albig and Doenecke (1997) designated
this gene H3/d.

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3E genes. They noted that all H3 genes in histone
gene cluster-1 (HIST1), including HIST1H3E, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig, Albig et al. (1997) mapped the H3/d gene to
chromosome 6p21.3, within a cluster of 35 histone genes.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3E.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

*FIELD* RF
1. Albig, W.; Doenecke, D.: The human histone gene cluster at the
D6S105 locus. Hum. Genet. 101: 284-294, 1997.

2. Albig, W.; Kardalinou, E.; Drabent, B.; Zimmer, A.; Doenecke, D.
: Isolation and characterization of two human H1 histone genes within
clusters of core histone genes. Genomics 10: 940-948, 1991.

3. Albig, W.; Kioschis, P.; Poustka, A.; Meergans, K.; Doenecke, D.
: Human histone gene organization: nonregular arrangement within a
large cluster. Genomics 40: 314-322, 1997.

4. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

*FIELD* CN
Matthew B. Gross - updated: 02/04/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
mgross: 02/04/2013
mgross: 7/22/2010
tkritzer: 4/3/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602814
*RECORD*
*FIELD* NO
602814
*FIELD* TI
*602814 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER I; HIST1H3I
;;HISTONE GENE CLUSTER 1, H3I;;
read moreHIST1 CLUSTER, H3I;;
H3 HISTONE FAMILY, MEMBER F; H3FF;;
H3/F
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

Albig et al. (1997) identified a gene, designated H3/f, encoding a
member of the H3 class of histones.

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3I genes. They noted that all H3 genes in histone
gene cluster-1 (HIST1), including HIST1H3I, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig from chromosome 6p22-p21.3, Albig and
Doenecke (1997) characterized a second cluster of 16 histone genes,
including H3/f, located 2 Mb centromeric to the major histone gene
cluster.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3I.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

*FIELD* RF
1. Albig, W.; Doenecke, D.: The human histone gene cluster at the
D6S105 locus. Hum. Genet. 101: 284-294, 1997.

2. Albig, W.; Meergans, T.; Doenecke, D.: Characterization of the
H1.5 gene completes the set of human H1 subtype genes. Gene 184:
141-148, 1997.

3. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

*FIELD* CN
Matthew B. Gross - updated: 02/04/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
mgross: 02/04/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602815
*RECORD*
*FIELD* NO
602815
*FIELD* TI
*602815 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER G; HIST1H3G
;;HISTONE GENE CLUSTER 1, H3G;;
read moreHIST1 CLUSTER, H3G;;
H3 HISTONE FAMILY, MEMBER H; H3FH;;
H3/H
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3G genes. They noted that all H3 genes in histone
gene cluster-1 (HIST1), including HIST1H3G, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes that included H3/h.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3G.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

*FIELD* RF
1. Albig, W.; Kioschis, P.; Poustka, A.; Meergans, K.; Doenecke, D.
: Human histone gene organization: nonregular arrangement within a
large cluster. Genomics 40: 314-322, 1997.

2. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

*FIELD* CN
Matthew B. Gross - updated: 02/04/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
mgross: 02/04/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602816
*RECORD*
*FIELD* NO
602816
*FIELD* TI
*602816 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER F; HIST1H3F
;;HISTONE GENE CLUSTER 1, H3F;;
read moreHIST1 CLUSTER, H3F;;
H3 HISTONE FAMILY, MEMBER I; H3FI;;
H3/I
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3F genes. They noted that all H3 genes in histone
gene cluster-1 (HIST1), including HIST1H3F, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes that included H3/i.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3F.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

*FIELD* RF
1. Albig, W.; Kioschis, P.; Poustka, A.; Meergans, K.; Doenecke, D.
: Human histone gene organization: nonregular arrangement within a
large cluster. Genomics 40: 314-322, 1997.

2. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

*FIELD* CN
Matthew B. Gross - updated: 02/04/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
mgross: 02/04/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602817
*RECORD*
*FIELD* NO
602817
*FIELD* TI
*602817 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER J; HIST1H3J
;;HISTONE GENE CLUSTER 1, H3J;;
read moreHIST1 CLUSTER, H3J;;
H3 HISTONE FAMILY, MEMBER J; H3FJ;;
H3/J
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
human HIST1H3J gene. They noted that all H3 genes in histone gene
cluster-1 (HIST1), including HIST1H3J, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig from chromosome 6p22-p21.3, Albig and
Doenecke (1997) characterized a second cluster of 16 histone genes,
including H3/j, located 2 Mb centromeric to the major histone gene
cluster.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3J.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

*FIELD* RF
1. Albig, W.; Doenecke, D.: The human histone gene cluster at the
D6S105 locus. Hum. Genet. 101: 284-294, 1997.

2. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

*FIELD* CN
Matthew B. Gross - updated: 02/04/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
mgross: 02/04/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602818
*RECORD*
*FIELD* NO
602818
*FIELD* TI
*602818 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER H; HIST1H3H
;;HISTONE GENE CLUSTER 1, H3H;;
read moreHIST1 CLUSTER, H3H;;
H3 HISTONE FAMILY, MEMBER K; H3FK;;
H3/K
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3H genes. They noted that all H3 genes in histone
gene cluster-1 (HIST1), including HIST1H3H, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig from chromosome 6p22-p21.3, Albig and
Doenecke (1997) characterized a second cluster of 16 histone genes,
including H3/k, located 2 Mb centromeric to the major histone gene
cluster.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3H.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

*FIELD* RF
1. Albig, W.; Doenecke, D.: The human histone gene cluster at the
D6S105 locus. Hum. Genet. 101: 284-294, 1997.

2. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

*FIELD* CN
Matthew B. Gross - updated: 02/04/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
mgross: 02/04/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602819
*RECORD*
*FIELD* NO
602819
*FIELD* TI
*602819 HISTONE GENE CLUSTER 1, H3 HISTONE FAMILY, MEMBER B; HIST1H3B
;;HISTONE GENE CLUSTER 1, H3B;;
read moreHIST1 CLUSTER, H3B;;
H3 HISTONE FAMILY, MEMBER L; H3FL;;
H3/L
*FIELD* TX
For background information on histones, histone gene clusters, and the
H3 histone family, see HIST1H3A (602810).

CLONING

Zhong et al. (1983) identified a gene encoding a member of the H3 class
of histones. Albig and Doenecke (1997) designated this gene H3/l.

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H3B genes. They noted that all H3 genes in histone
gene cluster-1 (HIST1), including HIST1H3B, encode the same protein,
designated H3.1. H3.1 differs from H3.2, which is encoded by HIST2H3C
(142780), at only 1 residue, and from histone H3.3, which is encoded by
both H3F3A (601128) and H3F3B (601058), at a few residues.

MAPPING

By analysis of a YAC contig, Albig et al. (1997) mapped the H3/l gene to
6p21.3, within a cluster of 35 histone genes.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called HIST1,
contains 55 histone genes, including HIST1H3B.

GENE FUNCTION

See HIST1H3A (602810) for functional information on H3.1 and the H3
histone family.

MOLECULAR GENETICS

Wu et al. (2012) reported that a K27M mutation occurring in either H3F3A
or HIST1H3B was observed in 78% of diffuse intrinsic pontine gliomas
(DIPGs) and 22% of non-brain-stem gliomas.

Lewis et al. (2013) reported that human (DIPGs) containing the K27M
mutation in either histone H3.3 (H3F3A) or H3.1 (HIST1H3B) display
significantly lower overall amounts of H3 with trimethylated lysine-27
(H3K27me3) and that histone H3K27M transgenes are sufficient to reduce
the amounts of H3K27me3 in vitro and in vivo. Lewis et al. (2013) found
that H3K27M inhibits the enzymatic activity of the Polycomb repressive
complex-2 (PRC2) through interaction with the EZH2 (601573) subunit. In
addition, transgenes containing lysine-to-methionine substitutions at
other known methylated lysines (H3K9 and H3K36) are sufficient to cause
specific reduction in methylation through inhibition of SET domain
enzymes. Lewis et al. (2013) proposed that K-to-M substitutions may
represent a mechanism to alter epigenetic states in a variety of
pathologies.

*FIELD* RF
1. Albig, W.; Doenecke, D.: The human histone gene cluster at the
D6S105 locus. Hum. Genet. 101: 284-294, 1997.

2. Albig, W.; Kioschis, P.; Poustka, A.; Meergans, K.; Doenecke, D.
: Human histone gene organization: nonregular arrangement within a
large cluster. Genomics 40: 314-322, 1997.

3. Lewis, P. W.; Muller, M. M.; Koletsky, M. S.; Cordero, F.; Lin,
S.; Banaszynski, L. A.; Garcia, B. A.; Muir, T. W.; Becher, O. J.;
Allis, C. D.: Inhibition of PRC2 activity by a gain-of-function H3
mutation found in pediatric glioblastoma. Science 340: 857-861,
2013.

4. Marzluff, W. F.; Gongidi, P.; Woods, K. R.; Jin, J.; Maltais, L.
J.: The human and mouse replication-dependent histone genes. Genomics 80:
487-498, 2002.

5. Wu, G.; Broniscer, A.; McEachron, T. A.; Lu, C.; Paugh, B. S.;
Becksfort, J.; Qu, C.; Ding, L.; Huether, R.; Parker, M.; Zhang, J.;
Gajjar, A.; and 9 others: Somatic histone H3 alterations in pediatric
diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nature
Genet 44: 251-253, 2012.

6. Zhong, R.; Roeder, R. G.; Heintz, N.: The primary structure and
expression of four cloned human histone genes. Nucleic Acids Res. 11:
7409-7425, 1983.

*FIELD* CN
Ada Hamosh - updated: 06/24/2013
Matthew B. Gross - updated: 2/4/2013

*FIELD* CD
Rebekah S. Rasooly: 7/9/1998

*FIELD* ED
alopez: 06/24/2013
mgross: 2/4/2013
mgross: 7/22/2010
tkritzer: 4/3/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

RBCC Red Blood Cell Collection

Full text data of HIST1H3A