RBCC Red Blood Cell Collection

HIST1H4A (H4/O, H4FO) [Confidence: high (present in two of the MS resources)]
Histone H4
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00453473
IPI00453473 Histone H4 Histone H4, along with histone H3, plays a central role in nucleosome formation soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a Cytoplasmic and nuclear n/a expected molecular weight found in band at molecular weight

UniProt P62805
ID H4_HUMAN Reviewed; 103 AA.
AC P62805; A2VCL0; P02304; P02305; Q6DRA9; Q6FGB8; Q6NWP7;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=Histone H4;
GN Name=HIST1H4A; Synonyms=H4/A, H4FA;
GN and
GN Name=HIST1H4B; Synonyms=H4/I, H4FI;
GN and
GN Name=HIST1H4C; Synonyms=H4/G, H4FG;
GN and
GN Name=HIST1H4D; Synonyms=H4/B, H4FB;
GN and
GN Name=HIST1H4E; Synonyms=H4/J, H4FJ;
GN and
GN Name=HIST1H4F; Synonyms=H4/C, H4FC;
GN and
GN Name=HIST1H4H; Synonyms=H4/H, H4FH;
GN and
GN Name=HIST1H4I; Synonyms=H4/M, H4FM;
GN and
GN Name=HIST1H4J; Synonyms=H4/E, H4FE;
GN and
GN Name=HIST1H4K; Synonyms=H4/D, H4FD;
GN and
GN Name=HIST1H4L; Synonyms=H4/K, H4FK;
GN and
GN Name=HIST2H4A; Synonyms=H4/N, H4F2, H4FN, HIST2H4;
GN and
GN Name=HIST2H4B; Synonyms=H4/O, H4FO;
GN and
GN Name=HIST4H4;
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].
RX PubMed=6314274; DOI=10.1093/nar/11.20.7069;
RA Sierra F., Stein G., Stein J.;
RT "Structure and in vitro transcription of a human H4 histone gene.";
RL Nucleic Acids Res. 11:7069-7086(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3035717; DOI=10.1126/science.3035717;
RA Pauli U., Chrysogelos S., Stein G., Stein J., Nick H.;
RT "Protein-DNA interactions in vivo upstream of a cell cycle-regulated
RT human H4 histone gene.";
RL Science 236:1308-1311(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
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=7626218; DOI=10.1089/dna.1995.14.591;
RA Drabent B., Kardalinou E., Bode C., Doenecke D.;
RT "Association of histone H4 genes with the mammalian testis-specific
RT H1t histone gene.";
RL DNA Cell Biol. 14:591-597(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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] (HIST1H4A; HIST1H4B; HIST1H4C;
RP HIST1H4D; HIST1H4E; HIST1H4F; HIST1H4H; HIST1H4I; HIST1H4J; HIST1H4K;
RP HIST1H4L; HIST2H4A AND HIST4H4).
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8988030;
RA Akasaka T., Miura I., Takahashi N., Akasaka H., Yonetani N., Ohno H.,
RA Fukuhara S., Okuma M.;
RT "A recurring translocation, t(3;6)(q27;p21), in non-Hodgkin's lymphoma
RT results in replacement of the 5' regulatory region of BCL6 with a
RT novel H4 histone gene.";
RL Cancer Res. 57:7-12(1997).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15527963; DOI=10.1016/j.gene.2004.07.036;
RA Braastad C.D., Hovhannisyan H., van Wijnen A.J., Stein J.L.,
RA Stein G.S.;
RT "Functional characterization of a human histone gene cluster
RT duplication.";
RL Gene 342:35-40(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (HIST1H4F; HIST1H4H AND
RP HIST2H4A).
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] (HIST1H4A; HIST1H4B;
RP HIST1H4C; HIST1H4D; HIST1H4E; HIST1H4F; HIST1H4H; HIST1H4I; HIST1H4J;
RP HIST1H4K AND HIST1H4L).
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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum, Eye, and Placenta;
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 [15]
RP PROTEIN SEQUENCE OF 25-36; 47-56; 61-78 AND 81-93, AND MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [16]
RP ACETYLATION AT LYS-6; LYS-9; LYS-13 AND LYS-17.
RX PubMed=7664735;
RA O'Neill L.P., Turner B.M.;
RT "Histone H4 acetylation distinguishes coding regions of the human
RT genome from heterochromatin in a differentiation-dependent but
RT transcription-independent manner.";
RL EMBO J. 14:3946-3957(1995).
RN [17]
RP DNA-BINDING REGION.
RX PubMed=3340182; DOI=10.1038/331365a0;
RA Ebralidse K.K., Grachev S.A., Mirzabekov A.D.;
RT "A highly basic histone H4 domain bound to the sharply bent region of
RT nucleosomal DNA.";
RL Nature 331:365-367(1988).
RN [18]
RP ACETYLATION AT LYS-6; LYS-9; LYS-13 AND LYS-17.
RX PubMed=2474456; DOI=10.1016/0014-5793(89)80947-0;
RA Turner B.M., O'Neill L.P., Allan I.M.;
RT "Histone H4 acetylation in human cells. Frequency of acetylation at
RT different sites defined by immunolabeling with site-specific
RT antibodies.";
RL FEBS Lett. 253:141-145(1989).
RN [19]
RP METHYLATION AT ARG-4.
RX PubMed=11448779; DOI=10.1016/S0960-9822(01)00294-9;
RA Strahl B.D., Briggs S.D., Brame C.J., Caldwell J.A., Koh S.S., Ma H.,
RA Cook R.G., Shabanowitz J., Hunt D.F., Stallcup M.R., Allis C.D.;
RT "Methylation of histone H4 at arginine 3 occurs in vivo and is
RT mediated by the nuclear receptor coactivator PRMT1.";
RL Curr. Biol. 11:996-1000(2001).
RN [20]
RP METHYLATION AT ARG-4.
RX PubMed=11387442; DOI=10.1126/science.1060781;
RA Wang H., Huang Z.-Q., Xia L., Feng Q., Erdjument-Bromage H.,
RA Strahl B.D., Briggs S.D., Allis C.D., Wong J., Tempst P., Zhang Y.;
RT "Methylation of histone H4 at arginine 3 facilitating transcriptional
RT activation by nuclear hormone receptor.";
RL Science 293:853-857(2001).
RN [21]
RP INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, AND CHROMOSOMAL
RP TRANSLOCATION WITH BCL6.
RX PubMed=12414651;
RA Kurata M., Maesako Y., Ueda C., Nishikori M., Akasaka T., Uchiyama T.,
RA Ohno H.;
RT "Characterization of t(3;6)(q27;p21) breakpoints in B-cell non-
RT Hodgkin's lymphoma and construction of the histone H4/BCL6 fusion
RT gene, leading to altered expression of Bcl-6.";
RL Cancer Res. 62:6224-6230(2002).
RN [22]
RP METHYLATION AT LYS-21.
RX PubMed=12086618; DOI=10.1016/S1097-2765(02)00548-8;
RA Nishioka K., Rice J.C., Sarma K., Erdjument-Bromage H., Werner J.,
RA Wang Y., Chuikov S., Valenzuela P., Tempst P., Steward R., Lis J.T.,
RA Allis C.D., Reinberg D.;
RT "PR-Set7 is a nucleosome-specific methyltransferase that modifies
RT lysine 20 of histone H4 and is associated with silent chromatin.";
RL Mol. Cell 9:1201-1213(2002).
RN [23]
RP SUMOYLATION.
RX PubMed=14578449; DOI=10.1073/pnas.1735528100;
RA Shiio Y., Eisenman R.N.;
RT "Histone sumoylation is associated with transcriptional repression.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13225-13230(2003).
RN [24]
RP CITRULLINATION AT ARG-4, AND METHYLATION AT ARG-4.
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 [25]
RP METHYLATION AT LYS-21.
RX PubMed=15964846; DOI=10.1074/jbc.M501691200;
RA Yin Y., Liu C., Tsai S.N., Zhou B., Ngai S.M., Zhu G.;
RT "SET8 recognizes the sequence RHRK20VLRDN within the N terminus of
RT histone H4 and mono-methylates lysine 20.";
RL J. Biol. Chem. 280:30025-30031(2005).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-52, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(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 SER-2; LYS-13 AND LYS-17, PHOSPHORYLATION AT SER-2, AND
RP METHYLATION AT LYS-21.
RX PubMed=17967882; DOI=10.1128/MCB.01517-07;
RA Pesavento J.J., Yang H., Kelleher N.L., Mizzen C.A.;
RT "Certain and progressive methylation of histone H4 at lysine 20 during
RT the cell cycle.";
RL Mol. Cell. Biol. 28:468-486(2008).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP ACETYLATION AT LYS-92, AND UBIQUITINATION AT LYS-92.
RX PubMed=19818714; DOI=10.1016/j.molcel.2009.08.019;
RA Yan Q., Dutt S., Xu R., Graves K., Juszczynski P., Manis J.P.,
RA Shipp M.A.;
RT "BBAP monoubiquitylates histone H4 at lysine 91 and selectively
RT modulates the DNA damage response.";
RL Mol. Cell 36:110-120(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-9; LYS-13; LYS-17 AND
RP LYS-32, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48 AND TYR-52, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [36]
RP CROTONYLATION AT LYS-6; LYS-9 AND LYS-13.
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 [37]
RP PHOSPHORYLATION AT SER-48.
RX PubMed=21724829; DOI=10.1101/gad.2055511;
RA Kang B., Pu M., Hu G., Wen W., Dong Z., Zhao K., Stillman B.,
RA Zhang Z.;
RT "Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosome
RT assembly.";
RL Genes Dev. 25:1359-1364(2011).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [39]
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).
RN [40]
RP VARIANT [LARGE SCALE ANALYSIS] GLN-64.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
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 Q12830:BPTF; NbExp=3; IntAct=EBI-302023, EBI-1560273;
CC Q12830-4:BPTF; NbExp=16; IntAct=EBI-302023, EBI-4288838;
CC P25440:BRD2; NbExp=5; IntAct=EBI-302023, EBI-2874802;
CC P49450:CENPA; NbExp=4; IntAct=EBI-302023, EBI-1751979;
CC Q9NQ92:COPRS; NbExp=3; IntAct=EBI-302023, EBI-1642558;
CC P45481:Crebbp (xeno); NbExp=2; IntAct=EBI-302023, EBI-296306;
CC O14929:HAT1; NbExp=4; IntAct=EBI-302023, EBI-2339359;
CC Q13547:HDAC1; NbExp=2; IntAct=EBI-302023, EBI-301834;
CC O75164:KDM4A; NbExp=7; IntAct=EBI-302023, EBI-936709;
CC Q9Y468:L3MBTL1; NbExp=4; IntAct=EBI-302023, EBI-1265089;
CC P49736:MCM2; NbExp=3; IntAct=EBI-302023, EBI-374819;
CC P25205:MCM3; NbExp=2; IntAct=EBI-302023, EBI-355153;
CC P33992:MCM5; NbExp=2; IntAct=EBI-302023, EBI-359410;
CC Q9BVI0:PHF20; NbExp=3; IntAct=EBI-302023, EBI-2560802;
CC A8MW92:PHF20L1; NbExp=2; IntAct=EBI-302023, EBI-2560834;
CC O14744:PRMT5; NbExp=3; IntAct=EBI-302023, EBI-351098;
CC Q16576:RBBP7; NbExp=4; IntAct=EBI-302023, EBI-352227;
CC Q9NQR1:SETD8; NbExp=5; IntAct=EBI-302023, EBI-1268946;
CC Q9VK33:Sfmbt (xeno); NbExp=10; IntAct=EBI-302023, EBI-117801;
CC O60264:SMARCA5; NbExp=2; IntAct=EBI-302023, EBI-352588;
CC Q12888:TP53BP1; NbExp=8; IntAct=EBI-302023, EBI-396540;
CC P63104:YWHAZ; NbExp=3; IntAct=EBI-302023, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC -!- PTM: Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13
CC (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the
CC genome but not in heterochromatin.
CC -!- PTM: Citrullination at Arg-4 (H4R3ci) by PADI4 impairs
CC methylation.
CC -!- PTM: Monomethylation and asymmetric dimethylation at Arg-4
CC (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation
CC at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed
CC by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the
CC PRDM1/PRMT5 complex may play a crucial role in the germ-cell
CC lineage.
CC -!- PTM: Monomethylated, dimethylated or trimethylated at Lys-21
CC (H4K20me1, H4K20me2, H4K20me3). Monomethylation is performed by
CC SET8. Trimethylation is performed by SUV420H1 and SUV420H2 and
CC induces gene silencing.
CC -!- PTM: Phosphorylated by PAK2 at Ser-48 (H4S47ph). This
CC phosphorylation increases the association of H3.3-H4 with the
CC histone chaperone HIRA, thus promoting nucleosome assembly of
CC H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4.
CC -!- PTM: Ubiquitinated by the CUL4-DDB-RBX1 complex in response to
CC ultraviolet irradiation. This may weaken the interaction between
CC histones and DNA and facilitate DNA accessibility to repair
CC proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in
CC response to DNA damage. The exact role of H4K91ub1 in DNA damage
CC response is still unclear but it may function as a licensing
CC signal for additional histone H4 post-translational modifications
CC such as H4 Lys-21 methylation (H4K20me).
CC -!- PTM: Sumoylated, which is associated with transcriptional
CC repression.
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 -!- DISEASE: Note=Chromosomal aberrations involving HISTONE H4 is a
CC cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation
CC t(3;6)(q27;p21), with BCL6.
CC -!- SIMILARITY: Belongs to the histone H4 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI28106.1; Type=Frameshift; Positions=3;
CC -----------------------------------------------------------------------
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DR EMBL; X00038; CAA24918.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M16707; AAA52652.1; -; Genomic_DNA.
DR EMBL; M60749; AAA63188.1; -; Genomic_DNA.
DR EMBL; X60481; CAA43011.1; -; Genomic_DNA.
DR EMBL; X60482; CAA43012.1; -; Genomic_DNA.
DR EMBL; X60483; CAA43013.1; -; Genomic_DNA.
DR EMBL; X60484; CAA43014.1; -; Genomic_DNA.
DR EMBL; X60486; CAA43016.1; -; Genomic_DNA.
DR EMBL; X60487; CAA43017.1; -; Genomic_DNA.
DR EMBL; X67081; CAA47464.1; -; Genomic_DNA.
DR EMBL; Z80787; CAB02549.1; -; Genomic_DNA.
DR EMBL; X83548; CAA58538.1; -; Genomic_DNA.
DR EMBL; AF525682; AAM83108.1; -; Genomic_DNA.
DR EMBL; AY128653; AAN01438.1; -; Genomic_DNA.
DR EMBL; AY128654; AAN01439.1; -; Genomic_DNA.
DR EMBL; AY128655; AAN01440.1; -; Genomic_DNA.
DR EMBL; AY128656; AAN01441.1; -; Genomic_DNA.
DR EMBL; AY128657; AAN01442.1; -; Genomic_DNA.
DR EMBL; AY128658; AAN01443.1; -; Genomic_DNA.
DR EMBL; AY128659; AAN01444.1; -; Genomic_DNA.
DR EMBL; AY128661; AAN01446.1; -; Genomic_DNA.
DR EMBL; AY128662; AAN01447.1; -; Genomic_DNA.
DR EMBL; AY128663; AAN01448.1; -; Genomic_DNA.
DR EMBL; AY128664; AAN01449.1; -; Genomic_DNA.
DR EMBL; AY128665; AAN01450.1; -; Genomic_DNA.
DR EMBL; AB000905; BAA19208.1; -; Genomic_DNA.
DR EMBL; AY648850; AAT68253.1; -; Genomic_DNA.
DR EMBL; CR542169; CAG46966.1; -; mRNA.
DR EMBL; CR542172; CAG46969.1; -; mRNA.
DR EMBL; CR542180; CAG46977.1; -; mRNA.
DR EMBL; CR542187; CAG46984.1; -; mRNA.
DR EMBL; CR542189; CAG46986.1; -; mRNA.
DR EMBL; AL021807; CAA16946.1; -; Genomic_DNA.
DR EMBL; AL021917; CAC69642.1; -; Genomic_DNA.
DR EMBL; AL031777; CAC03414.1; -; Genomic_DNA.
DR EMBL; AL031777; CAC03418.1; -; Genomic_DNA.
DR EMBL; AL049822; CAC03426.1; -; Genomic_DNA.
DR EMBL; AL049822; CAC03427.1; -; Genomic_DNA.
DR EMBL; AL353759; CAC04128.1; -; Genomic_DNA.
DR EMBL; Z98744; CAD24074.1; -; Genomic_DNA.
DR EMBL; AL591493; CAI12560.1; -; Genomic_DNA.
DR EMBL; AL591493; CAI12567.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55509.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55510.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55538.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55549.1; -; Genomic_DNA.
DR EMBL; CH471087; EAW55555.1; -; Genomic_DNA.
DR EMBL; CH471094; EAW96325.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03086.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03111.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03112.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03121.1; -; Genomic_DNA.
DR EMBL; BC017361; AAH17361.1; -; mRNA.
DR EMBL; BC054014; AAH54014.1; -; mRNA.
DR EMBL; BC066248; AAH66248.1; -; mRNA.
DR EMBL; BC066249; AAH66249.1; -; mRNA.
DR EMBL; BC066250; AAH66250.1; -; mRNA.
DR EMBL; BC067495; AAH67495.1; -; mRNA.
DR EMBL; BC067496; AAH67496.1; -; mRNA.
DR EMBL; BC067497; AAH67497.1; -; mRNA.
DR EMBL; BC069288; AAH69288.1; -; mRNA.
DR EMBL; BC069392; AAH69392.1; -; mRNA.
DR EMBL; BC069467; AAH69467.1; -; mRNA.
DR EMBL; BC069654; AAH69654.1; -; mRNA.
DR EMBL; BC093763; AAH93763.1; -; mRNA.
DR EMBL; BC093765; AAH93765.1; -; mRNA.
DR EMBL; BC093969; AAH93969.1; -; mRNA.
DR EMBL; BC111093; AAI11094.1; -; mRNA.
DR EMBL; BC111434; AAI11435.1; -; mRNA.
DR EMBL; BC112193; AAI12194.1; -; mRNA.
DR EMBL; BC120939; AAI20940.1; -; mRNA.
DR EMBL; BC128104; AAI28105.1; -; mRNA.
DR EMBL; BC128105; AAI28106.1; ALT_FRAME; mRNA.
DR EMBL; BC130558; AAI30559.1; -; mRNA.
DR EMBL; BC130560; AAI30561.1; -; mRNA.
DR EMBL; BC143045; AAI43046.1; -; mRNA.
DR PIR; D40335; HSHU4.
DR RefSeq; NP_001029249.1; NM_001034077.4.
DR RefSeq; NP_003486.1; NM_003495.2.
DR RefSeq; NP_003529.1; NM_003538.3.
DR RefSeq; NP_003530.1; NM_003539.3.
DR RefSeq; NP_003531.1; NM_003540.3.
DR RefSeq; NP_003532.1; NM_003541.2.
DR RefSeq; NP_003533.1; NM_003542.3.
DR RefSeq; NP_003534.1; NM_003543.3.
DR RefSeq; NP_003535.1; NM_003544.2.
DR RefSeq; NP_003536.1; NM_003545.3.
DR RefSeq; NP_003537.1; NM_003546.2.
DR RefSeq; NP_003539.1; NM_003548.2.
DR RefSeq; NP_068803.1; NM_021968.3.
DR RefSeq; NP_778224.1; NM_175054.2.
DR RefSeq; XP_005245367.1; XM_005245310.1.
DR RefSeq; XP_005245368.1; XM_005245311.1.
DR RefSeq; XP_005245369.1; XM_005245312.1.
DR RefSeq; XP_005245579.1; XM_005245522.1.
DR RefSeq; XP_005245580.1; XM_005245523.1.
DR RefSeq; XP_005245581.1; XM_005245524.1.
DR RefSeq; XP_005249493.1; XM_005249436.1.
DR RefSeq; XP_005249501.1; XM_005249444.1.
DR RefSeq; XP_005253358.1; XM_005253301.1.
DR RefSeq; XP_005277467.1; XM_005277410.1.
DR RefSeq; XP_005277468.1; XM_005277411.1.
DR RefSeq; XP_005277469.1; XM_005277412.1.
DR RefSeq; XP_005277485.1; XM_005277428.1.
DR RefSeq; XP_005277486.1; XM_005277429.1.
DR RefSeq; XP_005277487.1; XM_005277430.1.
DR UniGene; Hs.143080; -.
DR UniGene; Hs.247816; -.
DR UniGene; Hs.248172; -.
DR UniGene; Hs.248178; -.
DR UniGene; Hs.248179; -.
DR UniGene; Hs.278483; -.
DR UniGene; Hs.46423; -.
DR UniGene; Hs.528055; -.
DR UniGene; Hs.533295; -.
DR UniGene; Hs.55468; -.
DR UniGene; Hs.591790; -.
DR UniGene; Hs.655235; -.
DR UniGene; Hs.662174; -.
DR UniGene; Hs.706635; -.
DR UniGene; Hs.745457; -.
DR PDB; 2BQZ; X-ray; 1.50 A; B/F=18-26.
DR PDB; 2CV5; X-ray; 2.50 A; B/F=1-103.
DR PDB; 2KWN; NMR; -; B=10-24.
DR PDB; 2KWO; NMR; -; B=2-21.
DR PDB; 2LVM; NMR; -; B=15-28.
DR PDB; 2QQS; X-ray; 2.82 A; C/D=17-26.
DR PDB; 2RNY; NMR; -; B=14-28.
DR PDB; 2RS9; NMR; -; A=2-11.
DR PDB; 3A6N; X-ray; 2.70 A; B/F=1-103.
DR PDB; 3AFA; X-ray; 2.50 A; B/F=1-103.
DR PDB; 3AN2; X-ray; 3.60 A; B/F=1-103.
DR PDB; 3AV1; X-ray; 2.50 A; B/F=1-103.
DR PDB; 3AV2; X-ray; 2.80 A; B/F=1-103.
DR PDB; 3AYW; X-ray; 2.90 A; B/F=1-103.
DR PDB; 3AZE; X-ray; 3.00 A; B/F=1-103.
DR PDB; 3AZF; X-ray; 2.70 A; B/F=1-103.
DR PDB; 3AZG; X-ray; 2.40 A; B/F=1-103.
DR PDB; 3AZH; X-ray; 3.49 A; B/F=1-103.
DR PDB; 3AZI; X-ray; 2.70 A; B/F=1-103.
DR PDB; 3AZJ; X-ray; 2.89 A; B/F=1-103.
DR PDB; 3AZK; X-ray; 3.20 A; B/F=1-103.
DR PDB; 3AZL; X-ray; 2.70 A; B/F=1-103.
DR PDB; 3AZM; X-ray; 2.89 A; B/F=1-103.
DR PDB; 3AZN; X-ray; 3.00 A; B/F=1-103.
DR PDB; 3CFS; X-ray; 2.40 A; E=28-42.
DR PDB; 3CFV; X-ray; 2.60 A; E/F=25-42.
DR PDB; 3F9W; X-ray; 1.60 A; E/F/G/H=16-25.
DR PDB; 3F9X; X-ray; 1.25 A; E/F/G/H=16-25.
DR PDB; 3F9Y; X-ray; 1.50 A; E/F=16-25.
DR PDB; 3F9Z; X-ray; 1.60 A; E/F/G/H=16-25.
DR PDB; 3NQJ; X-ray; 2.10 A; B=21-103.
DR PDB; 3NQU; X-ray; 2.50 A; B=1-103.
DR PDB; 3O36; X-ray; 1.70 A; D/E=15-20.
DR PDB; 3QZS; X-ray; 1.80 A; C/D=13-22.
DR PDB; 3QZT; X-ray; 1.50 A; B=13-22.
DR PDB; 3QZV; X-ray; 2.00 A; C=8-18.
DR PDB; 3R45; X-ray; 2.60 A; B=1-103.
DR PDB; 3UVW; X-ray; 1.37 A; B=2-12.
DR PDB; 3UVX; X-ray; 1.91 A; B=12-22.
DR PDB; 3UVY; X-ray; 2.02 A; B=16-26.
DR PDB; 3UW9; X-ray; 2.30 A; E/F=8-18.
DR PDB; 3W96; X-ray; 3.00 A; B/F=1-103.
DR PDB; 3W97; X-ray; 3.20 A; B/F=1-103.
DR PDB; 3W98; X-ray; 3.42 A; B/F=1-103.
DR PDB; 3W99; X-ray; 3.00 A; B/F=17-103.
DR PDB; 4GQB; X-ray; 2.06 A; C=2-22.
DR PDB; 4H9N; X-ray; 1.95 A; B=2-103.
DR PDB; 4H9O; X-ray; 2.05 A; B=2-103.
DR PDB; 4H9P; X-ray; 2.20 A; B=2-103.
DR PDB; 4H9Q; X-ray; 1.95 A; B=2-103.
DR PDB; 4H9R; X-ray; 2.20 A; B=2-103.
DR PDB; 4H9S; X-ray; 2.60 A; C/D=21-103.
DR PDB; 4HGA; X-ray; 2.80 A; C=1-103.
DR PDBsum; 2BQZ; -.
DR PDBsum; 2CV5; -.
DR PDBsum; 2KWN; -.
DR PDBsum; 2KWO; -.
DR PDBsum; 2LVM; -.
DR PDBsum; 2QQS; -.
DR PDBsum; 2RNY; -.
DR PDBsum; 2RS9; -.
DR PDBsum; 3A6N; -.
DR PDBsum; 3AFA; -.
DR PDBsum; 3AN2; -.
DR PDBsum; 3AV1; -.
DR PDBsum; 3AV2; -.
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; 3CFS; -.
DR PDBsum; 3CFV; -.
DR PDBsum; 3F9W; -.
DR PDBsum; 3F9X; -.
DR PDBsum; 3F9Y; -.
DR PDBsum; 3F9Z; -.
DR PDBsum; 3NQJ; -.
DR PDBsum; 3NQU; -.
DR PDBsum; 3O36; -.
DR PDBsum; 3QZS; -.
DR PDBsum; 3QZT; -.
DR PDBsum; 3QZV; -.
DR PDBsum; 3R45; -.
DR PDBsum; 3UVW; -.
DR PDBsum; 3UVX; -.
DR PDBsum; 3UVY; -.
DR PDBsum; 3UW9; -.
DR PDBsum; 3W96; -.
DR PDBsum; 3W97; -.
DR PDBsum; 3W98; -.
DR PDBsum; 3W99; -.
DR PDBsum; 4GQB; -.
DR PDBsum; 4H9N; -.
DR PDBsum; 4H9O; -.
DR PDBsum; 4H9P; -.
DR PDBsum; 4H9Q; -.
DR PDBsum; 4H9R; -.
DR PDBsum; 4H9S; -.
DR PDBsum; 4HGA; -.
DR ProteinModelPortal; P62805; -.
DR SMR; P62805; 21-102.
DR DIP; DIP-33079N; -.
DR IntAct; P62805; 90.
DR MINT; MINT-276350; -.
DR STRING; 9606.ENSP00000289352; -.
DR ChEMBL; CHEMBL5876; -.
DR PhosphoSite; P62805; -.
DR SWISS-2DPAGE; P62805; -.
DR PaxDb; P62805; -.
DR PeptideAtlas; P62805; -.
DR PRIDE; P62805; -.
DR DNASU; 8294; -.
DR DNASU; 8360; -.
DR DNASU; 8362; -.
DR DNASU; 8363; -.
DR DNASU; 8364; -.
DR DNASU; 8365; -.
DR DNASU; 8366; -.
DR DNASU; 8367; -.
DR DNASU; 8368; -.
DR DNASU; 8370; -.
DR Ensembl; ENST00000289352; ENSP00000289352; ENSG00000158406.
DR Ensembl; ENST00000340756; ENSP00000343282; ENSG00000188987.
DR Ensembl; ENST00000354348; ENSP00000346316; ENSG00000198339.
DR Ensembl; ENST00000355057; ENSP00000347168; ENSG00000197238.
DR Ensembl; ENST00000355981; ENSP00000348258; ENSG00000198558.
DR Ensembl; ENST00000357549; ENSP00000350159; ENSG00000197914.
DR Ensembl; ENST00000358064; ENSP00000350767; ENSG00000197837.
DR Ensembl; ENST00000359907; ENSP00000352980; ENSG00000196176.
DR Ensembl; ENST00000360441; ENSP00000353624; ENSG00000198518.
DR Ensembl; ENST00000369157; ENSP00000358153; ENSG00000182217.
DR Ensembl; ENST00000369165; ENSP00000358162; ENSG00000183941.
DR Ensembl; ENST00000377364; ENSP00000366581; ENSG00000124529.
DR Ensembl; ENST00000377727; ENSP00000366956; ENSG00000158406.
DR Ensembl; ENST00000377745; ENSP00000366974; ENSG00000198327.
DR Ensembl; ENST00000377803; ENSP00000367034; ENSG00000197061.
DR Ensembl; ENST00000392932; ENSP00000376663; ENSG00000182217.
DR Ensembl; ENST00000392933; ENSP00000376664; ENSG00000182217.
DR Ensembl; ENST00000392938; ENSP00000376668; ENSG00000183941.
DR Ensembl; ENST00000392939; ENSP00000376669; ENSG00000183941.
DR Ensembl; ENST00000539745; ENSP00000443017; ENSG00000197837.
DR GeneID; 121504; -.
DR GeneID; 554313; -.
DR GeneID; 8294; -.
DR GeneID; 8359; -.
DR GeneID; 8360; -.
DR GeneID; 8361; -.
DR GeneID; 8362; -.
DR GeneID; 8363; -.
DR GeneID; 8364; -.
DR GeneID; 8365; -.
DR GeneID; 8366; -.
DR GeneID; 8367; -.
DR GeneID; 8368; -.
DR GeneID; 8370; -.
DR KEGG; hsa:121504; -.
DR KEGG; hsa:554313; -.
DR KEGG; hsa:8294; -.
DR KEGG; hsa:8359; -.
DR KEGG; hsa:8360; -.
DR KEGG; hsa:8361; -.
DR KEGG; hsa:8362; -.
DR KEGG; hsa:8363; -.
DR KEGG; hsa:8364; -.
DR KEGG; hsa:8365; -.
DR KEGG; hsa:8366; -.
DR KEGG; hsa:8367; -.
DR KEGG; hsa:8368; -.
DR KEGG; hsa:8370; -.
DR UCSC; uc001ess.3; human.
DR CTD; 121504; -.
DR CTD; 554313; -.
DR CTD; 8294; -.
DR CTD; 8359; -.
DR CTD; 8360; -.
DR CTD; 8361; -.
DR CTD; 8362; -.
DR CTD; 8363; -.
DR CTD; 8364; -.
DR CTD; 8365; -.
DR CTD; 8366; -.
DR CTD; 8367; -.
DR CTD; 8368; -.
DR CTD; 8370; -.
DR GeneCards; GC01M149830; -.
DR GeneCards; GC01P149804; -.
DR GeneCards; GC06M026027; -.
DR GeneCards; GC06M026188; -.
DR GeneCards; GC06M026281; -.
DR GeneCards; GC06M027798; -.
DR GeneCards; GC06M027917; -.
DR GeneCards; GC06P026021; -.
DR GeneCards; GC06P026104; -.
DR GeneCards; GC06P026204; -.
DR GeneCards; GC06P026240; -.
DR GeneCards; GC06P027107; -.
DR GeneCards; GC06P027791; -.
DR GeneCards; GC12M014920; -.
DR HGNC; HGNC:4781; HIST1H4A.
DR HGNC; HGNC:4789; HIST1H4B.
DR HGNC; HGNC:4787; HIST1H4C.
DR HGNC; HGNC:4782; HIST1H4D.
DR HGNC; HGNC:4790; HIST1H4E.
DR HGNC; HGNC:4783; HIST1H4F.
DR HGNC; HGNC:4788; HIST1H4H.
DR HGNC; HGNC:4793; HIST1H4I.
DR HGNC; HGNC:4785; HIST1H4J.
DR HGNC; HGNC:4784; HIST1H4K.
DR HGNC; HGNC:4791; HIST1H4L.
DR HGNC; HGNC:4794; HIST2H4A.
DR HGNC; HGNC:29607; HIST2H4B.
DR HGNC; HGNC:20510; HIST4H4.
DR HPA; CAB011503; -.
DR HPA; CAB021887; -.
DR HPA; CAB037279; -.
DR HPA; HPA042201; -.
DR MIM; 142750; gene.
DR MIM; 602822; gene.
DR MIM; 602823; gene.
DR MIM; 602824; gene.
DR MIM; 602825; gene.
DR MIM; 602826; gene.
DR MIM; 602827; gene.
DR MIM; 602828; gene.
DR MIM; 602829; gene.
DR MIM; 602830; gene.
DR MIM; 602831; gene.
DR MIM; 602833; gene.
DR MIM; 615069; gene.
DR neXtProt; NX_P62805; -.
DR PharmGKB; PA29169; -.
DR eggNOG; COG2036; -.
DR HOGENOM; HOG000234654; -.
DR HOVERGEN; HBG051878; -.
DR InParanoid; P62805; -.
DR KO; K11254; -.
DR OMA; YEEVRVV; -.
DR OrthoDB; EOG77T174; -.
DR PhylomeDB; P62805; -.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_120956; Cellular responses to stress.
DR EvolutionaryTrace; P62805; -.
DR GeneWiki; HIST1H4A; -.
DR GeneWiki; HIST1H4B; -.
DR GeneWiki; HIST1H4C; -.
DR GeneWiki; HIST1H4D; -.
DR GeneWiki; HIST1H4E; -.
DR GeneWiki; HIST1H4F; -.
DR GeneWiki; HIST1H4H; -.
DR GeneWiki; HIST1H4I; -.
DR GeneWiki; HIST1H4J; -.
DR GeneWiki; HIST1H4K; -.
DR GeneWiki; HIST1H4L; -.
DR GeneWiki; HIST2H4A; -.
DR GeneWiki; HIST4H4; -.
DR NextBio; 31093; -.
DR PRO; PR:P62805; -.
DR ArrayExpress; P62805; -.
DR Bgee; P62805; -.
DR CleanEx; HS_HIST1H4A; -.
DR CleanEx; HS_HIST1H4B; -.
DR CleanEx; HS_HIST1H4C; -.
DR CleanEx; HS_HIST1H4D; -.
DR CleanEx; HS_HIST1H4E; -.
DR CleanEx; HS_HIST1H4F; -.
DR CleanEx; HS_HIST1H4H; -.
DR CleanEx; HS_HIST1H4I; -.
DR CleanEx; HS_HIST1H4L; -.
DR CleanEx; HS_HIST2H4A; -.
DR CleanEx; HS_HIST2H4B; -.
DR CleanEx; HS_HIST4H4; -.
DR Genevestigator; P62805; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000786; C:nucleosome; TAS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; TAS:UniProtKB.
DR GO; GO:0034080; P:CENP-A containing nucleosome assembly at centromere; TAS:Reactome.
DR GO; GO:0045653; P:negative regulation of megakaryocyte differentiation; IDA:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; NAS:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; TAS:Reactome.
DR Gene3D; 1.10.20.10; -; 1.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR007125; Histone_core_D.
DR InterPro; IPR001951; Histone_H4.
DR InterPro; IPR019809; Histone_H4_CS.
DR Pfam; PF00125; Histone; 1.
DR PRINTS; PR00623; HISTONEH4.
DR SMART; SM00417; H4; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR PROSITE; PS00047; HISTONE_H4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosomal rearrangement; Chromosome;
KW Citrullination; Complete proteome; Direct protein sequencing;
KW DNA-binding; Isopeptide bond; Methylation; Nucleosome core; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 103 Histone H4.
FT /FTId=PRO_0000158320.
FT DNA_BIND 17 21
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 4 4 Asymmetric dimethylarginine; by PRMT1;
FT alternate.
FT MOD_RES 4 4 Citrulline; alternate.
FT MOD_RES 4 4 Omega-N-methylarginine; by PRMT1;
FT alternate.
FT MOD_RES 4 4 Symmetric dimethylarginine; by PRMT5 and
FT PRMT7; alternate (By similarity).
FT MOD_RES 6 6 N6-acetyllysine; alternate.
FT MOD_RES 6 6 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 9 9 N6-acetyllysine; alternate.
FT MOD_RES 9 9 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 13 13 N6-acetyllysine; alternate.
FT MOD_RES 13 13 N6-crotonyl-L-lysine; alternate.
FT MOD_RES 17 17 N6-acetyllysine; alternate.
FT MOD_RES 17 17 N6-crotonyl-L-lysine; alternate (By
FT similarity).
FT MOD_RES 21 21 N6,N6,N6-trimethyllysine; alternate.
FT MOD_RES 21 21 N6,N6-dimethyllysine; alternate.
FT MOD_RES 21 21 N6-methyllysine; alternate.
FT MOD_RES 32 32 N6-acetyllysine.
FT MOD_RES 48 48 Phosphoserine; by PAK2.
FT MOD_RES 52 52 Phosphotyrosine.
FT MOD_RES 89 89 Phosphotyrosine (By similarity).
FT MOD_RES 92 92 N6-acetyllysine; alternate.
FT CROSSLNK 92 92 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT VARIANT 64 64 E -> Q (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036206.
FT CONFLICT 71 71 V -> A (in Ref. 14; AAH67496).
FT CONFLICT 77 77 A -> P (in Ref. 11; CAG46986).
FT STRAND 6 9
FT STRAND 21 23
FT STRAND 28 30
FT HELIX 32 41
FT STRAND 45 47
FT HELIX 49 76
FT STRAND 80 82
FT HELIX 84 91
FT STRAND 94 96
FT TURN 97 102
SQ SEQUENCE 103 AA; 11367 MW; A9E5DFD3F8B97598 CRC64;
MSGRGKGGKG LGKGGAKRHR KVLRDNIQGI TKPAIRRLAR RGGVKRISGL IYEETRGVLK
VFLENVIRDA VTYTEHAKRK TVTAMDVVYA LKRQGRTLYG FGG
//

MIM 142750
*RECORD*
*FIELD* NO
142750
*FIELD* TI
*142750 HISTONE GENE CLUSTER 2, H4 HISTONE FAMILY, MEMBER A; HIST2H4A
;;HISTONE GENE CLUSTER 2, H4A;;
read moreHIST2 CLUSTER, H4A;;
HIST2H4;;
H4 HISTONE FAMILY, MEMBER N; H4FN;;
H4 HISTONE, FAMILY 2; H4F2
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

By restriction endonuclease digestion of a genomic clone, Sierra et al.
(1983) isolated DNA (pF0108) with the capacity to code for a typical H4
histone protein, H4FN. Sequence analysis predicted a 103-amino acid
protein. Autoradiographic analysis of an in vitro transcribed pF0108
allowed visualization of a 2.9-kb transcript.

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST2H4A genes. All mouse and human H4 genes, including
HIST2H4A, encode the same protein.

GENE STRUCTURE

Sierra et al. (1983) found that H4FN has a 5-prime promoter containing
regulatory sequences typically used by RNA polymerase II. The H4FN gene
contains no intervening sequences. Sierra et al. (1983) predicted the
termination of the mRNA at the ACCA motif just downstream from the
hyphenated dyad symmetry characteristic of other histone genes.

Pauli et al. (1987) identified 2 regions of DNA with 4 potential
protein-binding domains in the 5-prime promoter region of H4FN that are
protected from reaction with dimethyl sulfate in cells and from
digestion with DNase I in nuclei.

MAPPING

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 1q21, which they called histone gene
cluster-2 (HIST2), contains 6 histone genes, including HIST2H4A.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*FIELD* RF
1. 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.

2. Pauli, U.; Chrysogelos, S.; Stein, G.; Stein, J.; Nick, H.: Protein-DNA
interactions in vivo upstream of a cell cycle-regulated human H4 histone
gene. Science 236: 1308-1311, 1987.

3. Sierra, F.; Stein, G.; Stein, J.: Structure and in vitro transcription
of a human H4 histone gene. Nucleic Acids Res. 11: 7069-7086, 1983.

*FIELD* CN
Matthew B. Gross - updated: 02/07/2013
Ada Hamosh - updated: 8/17/2010
Ada Hamosh - updated: 4/18/2006
Victor A. McKusick - updated: 3/29/2005

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
mgross: 02/07/2013
mgross: 1/29/2013
mgross: 1/11/2013
alopez: 12/21/2012
terry: 12/13/2012
alopez: 8/20/2010
terry: 8/17/2010
mgross: 7/22/2010
alopez: 3/25/2008
terry: 3/6/2008
alopez: 4/24/2006
terry: 4/18/2006
tkritzer: 4/1/2005
terry: 3/29/2005
alopez: 10/4/2004
tkritzer: 9/28/2004
alopez: 9/16/2003
carol: 3/28/2003
terry: 11/15/2001
alopez: 7/10/1998
psherman: 4/28/1998
mark: 9/22/1996
mimadm: 4/29/1994
warfield: 4/8/1994
supermim: 3/16/1992
carol: 2/14/1992
supermim: 3/20/1990
ddp: 10/27/1989

MIM 602822
*RECORD*
*FIELD* NO
602822
*FIELD* TI
*602822 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER A; HIST1H4A
;;HISTONE GENE CLUSTER 1, H4A;;
read moreHIST1 CLUSTER, H4A;;
H4 HISTONE FAMILY, MEMBER A; H4FA;;
H4/A
*FIELD* TX

DESCRIPTION

The nucleosome is the basic repeat unit of eukaryotic chromatin. The
nucleosome core particle consists of an octamer formed by 2 each of the
core histones H2A (see 613499), H2B (see 609904), H3 (see 602810), and
H4, around which DNA is wrapped. A fifth histone, histone H1 (see
142709), is bound to the linker DNA between nucleosomes and is important
for the higher order structure of chromatin. HIST1H4A is a core histone
H4 (summary by Marzluff et al. (2002) and Foster and Downs (2005)).

GENE FAMILY

All core histones, including H4 histones, contain a histone fold domain,
which is central to the nucleosome core structure, and a flexible
N-terminal domain that protrudes from the nucleosome core particle. Like
other histones, H4 histones can be subgrouped according to their
temporal expression. Replication-dependent histones, such as HIST1H4A
through HIST1H4L (602831) and HIST2H4A (142750) are mainly expressed
during S phase. In contrast, replication-independent histones, or
replacement variant histones, can be expressed throughout the cell
cycle. Most replication-dependent H4 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. HIST2 contains 1
replication-dependent H4 gene, HIST2H4A, and there are no H4 genes in
HIST3. An additional H4 gene, HIST4H4 (615069), is located on chromosome
12p13.1. 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 human and mouse H4 histone genes encode
the same protein (summary by Marzluff et al. (2002) and Foster and Downs
(2005)).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4A genes. All mouse and human H4 genes, including
HIST1H4A, encode the same protein.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes, including H4/a.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
HIST1 cluster on chromosome 6p22-p21 contains 55 histone genes,
including 12 H4 genes. The HIST1H4A gene is the most telomeric H4 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 H4 gene (HIST2H4A; 142750), and the HIST3 cluster on
chromosome 1q42 contains 3 histone genes, but no H4 genes. Hist2 and
Hist3 are located on mouse chromosomes 3F1-F2 and 11B2, respectively. An
additional H4 gene, HIST4H4 (615069), is located on human chromosome
12p13.1 and mouse chromosome 6G1.

GENE FUNCTION

- H4 Histone Family

As reviewed by Felsenfeld (1992), detailed biochemical definition of the
protein complexes that regulate gene transcription led to reemergence of
questions concerning the role of histones. He reviewed evidence
suggesting that transcriptional activation requires that transcription
factors successfully compete with histones for binding to promoters.

CpG island hypermethylation and global genomic hypomethylation are
common epigenetic features of cancer cells. Fraga et al. (2005)
characterized posttranslational modifications to histone H4 in a
comprehensive panel of normal tissues, cancer cell lines, and primary
tumors. They found that cancer cells had a loss of monoacetylated and
trimethylated forms of histone H4. These changes appeared early and
accumulated during the tumorigenic process, as they showed in a mouse
model of multistage skin carcinogenesis. The losses occurred
predominantly at the acetylated lys16 and trimethylated lys20 residues
of histone H4 and were associated with the hypomethylation of DNA
repetitive sequences, a well-known characteristic of cancer cells. Fraga
et al. (2005) suggested that the global loss of monoacetylation and
trimethylation of histone H4 is a common hallmark of human tumor cells.

Wang et al. (2001) reported the purification, molecular identification,
and functional characterization of a histone H4-specific
methyltransferase, PRMT1 (602950), a protein arginine methyltransferase.
PRMT1 specifically methylates arginine-3 of histone H4 in vitro and in
vivo. Methylation of arg3 by PRMT1 facilitates subsequent acetylation of
H4 tails by p300 (602700). However, acetylation of H4 inhibits its
methylation by PRMT1. Most important, a mutation in the
S-adenosyl-L-methionine-binding site of PRMT1 substantially crippled its
nuclear receptor coactivator activity. Wang et al. (2001) concluded that
their findings reveal arg3 of H4 as a novel methylation site by PRMT1
and indicate that arg3 methylation plays an important role in
transcriptional regulation.

Agalioti et al. (2002) found that only a small subset of lysines in
histones H3 (see 602810) 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.

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.

Acetylation of histone H4 on lysine-16 (H4-K16Ac) is a prevalent and
reversible posttranslational chromatin modification in eukaryotes. To
characterize the structural and functional role of this mark,
Shogren-Knaak et al. (2006) used a native chemical ligation strategy to
generate histone H4 that was homogeneously acetylated at K16. The
incorporation of this modified histone into nucleosomal arrays inhibited
the formation of compact 30-nanometer-like fibers and impeded the
ability of chromatin to form cross-fiber interactions. H4-K16Ac also
inhibited the ability of the adenosine triphosphate-utilizing chromatin
assembly and remodeling enzyme ACF to mobilize a mononucleosome,
indicating that this single histone modification modulates both higher
order chromatin structure and functional interactions between a
nonhistone protein and the chromatin fiber.

In a screen for endogenous tumor-associated T-cell responses in a
primary mouse model of prostatic adenocarcinoma, Savage et al. (2008)
identified a naturally arising CD8+ T cell response that is reactive to
a peptide derived from histone H4. Despite the ubiquitous nature of
histones, T cell recognition of histone H4 peptide was specifically
associated with the presence of prostate cancer in these mice. Thus,
Savage et al. (2008) concluded that the repertoire of antigens
recognized by tumor-infiltrating T cells is broader than previously
thought and includes peptides derived from ubiquitous self antigens that
are normally sequestered from immune detection.

Dang et al. (2009) reported an age-associated decrease in yeast Sir2
(see SIRT1, 604479) protein abundance accompanied by an increase in
histone H4 lysine-16 acetylation and loss of histones at specific
subtelomeric regions in replicatively old yeast cells, which results in
compromised transcriptional silencing at these loci. Antagonizing
activities of Sir2 and Sas2, a histone acetyltransferase, regulate the
replicative life span through histone H4 lys16 at subtelomeric regions.
Dang et al. (2009) concluded that this pathway, distinct from existing
aging models for yeast, may represent an evolutionarily conserved
function of sirtuins in regulation of replicative aging by maintenance
of intact telomeric chromatin.

Xu et al. (2010) reported that significant amounts of histone H3.3 (see
601128)-H4 tetramers split in vivo, whereas most H3.1 (see 602810)-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.

Qi et al. (2010) provided multiple lines of evidence establishing PHF8
(300560) as the first monomethyl histone H4 lysine-20 (H4K20me1)
demethylase, with additional activities towards histone H3K9me1 and me2.
PHF8 is located around the transcriptional start sites of approximately
7,000 RefSeq genes and in gene bodies and intergenic regions. PHF8
depletion resulted in upregulation of H4K20me1 and H3K9me1 at the
transcriptional start site and H3K9me2 in the nontranscriptional start
sites, respectively, demonstrating differential substrate specificities
at different target locations. PHF8 positively regulates gene
expression, which is dependent on its H3K4me3-binding PHD and catalytic
domains. Importantly, patient mutations significantly compromised PHF8
catalytic function. PHF8 regulates cell survival in the zebrafish brain
and jaw development, thus providing a potentially relevant biologic
context for understanding the clinical symptoms associated with PHF8
patients. Lastly, genetic and molecular evidence supported a model
whereby PHF8 regulates zebrafish neuronal cell survival and jaw
development in part by directly regulating the expression of the
homeodomain transcription factor MSX1/MSXB (605558), which functions
downstream of multiple signaling and developmental pathways.

Liu et al. (2010) reported that PHF8, while using multiple substrates,
including H3K9me1/2 and H3K27me2, also functions as an H4K20me1
demethylase. PHF8 is recruited to promoters by its PHD domain based on
interaction with H3K4me2/3 and controls G1-S transition in conjunction
with E2F1, HCF1 (300019), and SET1A (611052), at least in part, by
removing the repressive H4K20me1 mark from a subset of E2F1-regulated
gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin
in prophase is apparently required for the accumulation of H4K20me1
during early mitosis, which might represent a component of the condensin
II loading process. Accordingly, the HEAT repeat clusters in 2
non-structural maintenance of chromosomes (SMC) condensin II subunits,
NCAPD3 (609276) and NCAPG2 (608532), are capable of recognizing
H4K20me1, and ChIP-Seq analysis demonstrated a significant overlap of
condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, Liu et al.
(2010) concluded that the identification and characterization of an
H4K20me1 demethylase, PHF8, has revealed an intimate link between this
enzyme and 2 distinct events in cell cycle progression.

Fullgrabe et al. (2013) reported that induction of autophagy is coupled
to reduction of histone H4 lysine-16 acetylation (H4K16ac) through
downregulation of the histone acetyltransferase MOF (MYST1; 609912), and
demonstrated that this histone modification regulates the outcome of
autophagy. At a genomewide level, Fullgrabe et al. (2013) found that
H4K16 deactylation is associated predominantly with the downregulation
of autophagy-related genes. Antagonizing H4K16ac downregulation upon
autophagy induction results in the promotion of cell death. Fullgrabe et
al. (2013) concluded that their findings established that alteration in
a specific histone posttranslational modification during autophagy
affects the transcriptional regulation of autophagy-related genes and
initiates a regulatory feedback loop, which serves as a key determinant
of survival versus death responses upon autophagy induction.

BIOCHEMICAL FEATURES

- Crystal Structure

Sekulic et al. (2010) reported the crystal structure of a subnucleosomal
heterotetramer, (CENP-A-H4)2 (CENP-A, 117139, in complex with histone
H4), that reveals 3 distinguishing properties encoded by the residues
that comprise the CENP-A targeting domain (CATD): (1) a CENP-A-CENP-A
interface that is substantially rotated relative to the H3-H3 interface;
(2) a protruding loop L1 of the opposite charge as that on H3; and (3)
strong hydrophobic contacts that rigidify the CENP-A-H4 interface.
Residues involved in the CENP-A-CENP-A rotation are required for
efficient incorporation into centromeric chromatin, indicating
specificity for an unconventional nucleosome shape. DNA topologic
analysis indicated that CENP-A-containing nucleosomes are octameric with
conventional left-handed DNA wrapping. Sekulic et al. (2010) concluded
that CENP-A marks centromere location by restructuring the nucleosome
from within its folded histone core.

Elsasser et al. (2012) reported the crystal structures of the DAXX
(603186) histone-binding domain with a histone H3.3-H4 dimer, including
mutants within DAXX and H3.3, together with in vitro and in vivo
functional studies that elucidated the principles underlying H3.3
recognition specificity. Occupying 40% of the histone surface-accessible
area, DAXX wraps around the H3.3-H4 dimer, with complex formation
accompanied by structural transitions in the H3.3-H4 histone fold. DAXX
uses an extended alpha-helical conformation to compete with major
interhistone, DNA, and ASF1 interaction sites. Elsasser et al. (2012)
concluded that their structural studies identified recognition elements
that read out H3.3-specific residues, and functional studies addressed
the contribution of gly90 in H3.3 and glu225 in DAXX to
chaperone-mediated H3.3 variant recognition specificity.

EVOLUTION

Histone IV genes are highly conserved across evolution. Delange and
Smith (1971) noted that, in their 110 amino acids, histone IV genes of
cattle and garden peas differ by only 2 residues.

Heintz et al. (1981) concluded that the human histone genes are
clustered in the genome but are not arranged into recognizable repeating
units. The lack of organization of the human histone genes (as
contrasted with those of invertebrates or of Xenopus laevis) may reflect
the diminished requirement for rapid synthesis of large quantities of
histone proteins during early mammalian development.

Kedes and Maxson (1981) found that the histone genes in man, mouse,
chicken, and toad show a dispersed topology; they are scattered and
separated by long stretches of nonhistone DNA. In an article subtitled
'Paradigm Lost,' the authors referred to 'this newly discovered
diaspora.'

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, HIST1H4A is the most telomeric
H4 gene within HIST1, and HIST1H4L (602831) 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.

HISTORY

Szabo et al. (1978) presented nucleic acid hybridization data indicating
that chromosome 7 carries gene(s) coding for histone H4 protein.
Steffensen (1979) presented evidence that all 5 histone genes in man are
clustered at 7q2. Yunis and Chandler (1979) located the histone genes to
bands 7q32-36 and the homologous chromosome segments in chimpanzee,
gorilla, and orangutan.

A clone containing a human histone gene cluster in the order
H3-H4-H1-H2A-H2B was isolated by Clark et al. (1981), as cited by
Hentschel and Birnstiel (1981). Sierra et al. (1982) likewise found an
arrangement of the histone genes different from that in the sea urchin
and Drosophila.

Carozzi et al. (1984) isolated an H1 histone gene from a 15-kb human DNA
genomic sequence. The presence of H2A, H2B, H3 and H4 genes in this same
15-kb fragment demonstrated that these genes are clustered.

By study of mouse-human cell hybrids and by in situ hybridization, Green
et al. (1984) showed that H3 and H4 histone genes are on 1q, probably
1q21. From in situ hybridization, Tripputi et al. (1986) concluded that
histone genes map to at least 3 different chromosomes: 1, 6, and 12.
Some may be nonexpressed pseudogenes. They commented that the number of
histone genes is between 100 and 200. The histones have the distinction
of being the only proteins coded by repetitive DNA. Tanguay et al.
(1987) reported in situ hybridization data corroborating those of
Tripputi et al. (1986), using a heterologous probe containing the 5
histone genes of Drosophila. They found that the main concentrations of
grains were at 6p12-q21, 12q11-q22, and 1cen-q25. Allen et al. (1989)
reported the conflicting assignment of histones 3 and 4 to human
chromosome 6.

*FIELD* SA
Chandler et al. (1979); Lichtler et al. (1982); Shogren-Knaak et al.
(2006)
*FIELD* RF
1. Agalioti, T.; Chen, G.; Thanos, D.: Deciphering the transcriptional
histone acetylation code for a human gene. Cell 111: 381-392, 2002.

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. Allen, B.; Ostrer, H.; Stein, J.; Stein, G.: Histone gene clusters
map to chromosomes 1 and 6. (Abstract) Cytogenet. Cell Genet. 51:
950 only, 1989.

4. Black, B. E.; Foltz, D. R.; Chakravarthy, S.; Luger, K.; Woods,
V. L., Jr.; Cleveland, D. W.: Structural determinants for generating
centromeric chromatin. Nature 430: 578-582, 2004.

5. Carozzi, N.; Marashi, F.; Plumb, M.; Zimmerman, S.; Zimmerman,
A.; Coles, L. S.; Wells, J. R. E.; Stein, G.; Stein, J.: Clustering
of human H1 and core histone genes. Science 224: 1115-1117, 1984.

6. Chandler, M. E.; Kedes, L. H.; Cohn, R. H.; Yunis, J. J.: Genes
coding for histone proteins in man are located on the distal end of
chromosome 7. Science 205: 908-910, 1979.

7. Clark, S. J.; Krieg, P. A.; Wells, J. R. E.: Isolation of a clone
containing human histone genes. Nucleic Acids Res. 9: 1583-1597,
1981.

8. Dang, W.; Steffen, K. K.; Perry, R.; Dorsey, J. A.; Johnson, F.
B.; Shilatifard, A.; Kaeberlein, M.; Kennedy, B. K.; Berger, S. L.
: Histone H4 lysine 16 acetylation regulates cellular lifespan. Nature 459:
802-807, 2009.

9. Delange, R. J.; Smith, E. L.: Histones: structure and function. Ann.
Rev. Biochem. 40: 279-314, 1971.

10. Elsasser, S. J.; Huang, H.; Lewis, P. W.; Chin, J. W.; Allis,
C. D.; Patel, D. J.: DAXX envelops a histone H3.3-H4 dimer for H3.3-specific
recognition. Nature 491: 560-565, 2012.

11. Felsenfeld, G.: Chromatin as an essential part of the transcriptional
mechanism. Nature 355: 219-224, 1992.

12. Foster, E. R.; Downs, J. A.: Histone H2A phosphorylation in DNA
double-strand break repair. FEBS J. 272: 3231-3240, 2005.

13. Fraga, M. F.; Ballestar, E.; Villar-Garea, A.; Boix-Chornet, M.;
Espada, J.; Schotta, G.; Bonaldi, T.; Haydon, C.; Ropero, S.; Petrie,
K.; Iyer, N. G.; Perez-Rosado, A.; and 11 others: Loss of acetylation
at lys16 and trimethylation at lys20 of histone H4 is a common hallmark
of human cancer. Nature Genet. 37: 391-400, 2005.

14. Fullgrabe, J.; Lynch-Day, M. A.; Heldring, N.; Li, W.; Struijk,
R. B.; Ma, Q.; Hermanson, O.; Rosenfeld, M. G.; Klionsky, D. J.; Joseph,
B.: The histone H4 lysine 16 acetyltransferase hMOF regulates the
outcome of autophagy. Nature 500: 468-471, 2013.

15. Green, L.; Van Antwerpen, R.; Stein, J.; Stein, G.; Tripputi,
P.; Emanuel, B.; Selden, J.; Croce, C.: A major human histone gene
cluster on the long arm of chromosome 1. Science 226: 838-840, 1984.

16. Heintz, N.; Zernik, M.; Roeder, R. G.: The structure of the human
histone genes: clustered but not tandemly repeated. Cell 24: 661-668,
1981.

17. Hentschel, C. C.; Birnstiel, M. L.: The organization and expression
of histone gene families. Cell 25: 301-313, 1981.

18. Kedes, L.; Maxson, R.: Histone gene organization: paradigm lost. Nature 2
94: 11-12, 1981.

19. Lichtler, A. C.; Sierra, F.; Clark, S.; Wells, J. R. E.; Stein,
J. L.; Stein, G. S.: Multiple H4 histone mRNAs of HeLa cells are
encoded in different genes. Nature 298: 195-198, 1982.

20. Liu, W.; Tanasa, B.; Tyurina, O. V.; Zhou, T. Y.; Gassmann, R.;
Liu, W. T.; Ohgi, K. A.; Benner, C.; Garcia-Bassets, I.; Aggarwal,
A. K.; Desai, A.; Dorrestein, P. C.; Glass, C. K.; Rosenfeld, M. G.
: PHF8 mediates histone H4 lysine 20 demethylation events involved
in cell cycle progression. Nature 466: 508-512, 2010.

21. 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.

22. Qi, H. H.; Sarkissian, M.; Hu, G.-Q.; Wang, Z.; Bhattacharjee,
A.; Gordon, D. B.; Gonzales, M.; Lan, F.; Ongusaha, P. P.; Huarte,
M.; Yaghi, N. K.; Lim, H.; Garcia, B. A.; Brizuela, L.; Zhao, K.;
Roberts, T. M.; Shi, Y.: Histone H4K20/H3K9 demethylase PHF8 regulates
zebrafish brain and craniofacial development. Nature 466: 503-507,
2010.

23. Savage, P. A.; Vosseller, K.; Kang, C.; Larimore, K.; Riedel,
E.; Wojnoonski, K.; Jungbluth, A. A.; Allison, J. P.: Recognition
of a ubiquitous self antigen by prostate cancer-infiltrating CD8+
T lymphocytes. Science 319: 215-220, 2008.

24. Sekulic, N.; Bassett, E. A.; Rogers, D. J.; Black, B. E.: The
structure of (CENP-A-H4)2 reveals physical features that mark centromeres. Nature 467:
347-351, 2010.

25. Shogren-Knaak, M.; Ishii, H.; Sun, J.-M.; Pazin, M. J.; Davie,
J. R.; Peterson, C. L.: Histone H4-K16 acetylation controls chromatin
structure and protein interactions. Science 311: 844-847, 2006.

26. Shogren-Knaak, M.; Ishii, H.; Sun, J.-M.; Pazin, M. J.; Davie,
J. R.; Peterson, C. L.: Histone H4-K16 acetylation controls chromatin
structure and protein interactions. Science 311: 844-847, 2006.

27. Sierra, F.; Lichtler, A.; Marashi, F.; Rickles, R.; Van Dyke,
T.; Clark, S.; Wells, J.; Stein, G.; Stein, J.: Organization of human
histone genes. Proc. Nat. Acad. Sci. 79: 1795-1799, 1982.

28. Steffensen, D. M.: Human histone genes mapped to chromosome 7.
(Abstract) Cytogenet. Cell Genet. 25: 211 only, 1979.

29. Szabo, P.; Yu, L. C.; Borun, T.; Varicchio, F.; Siniscalco, M.;
Prensky, W.: Localization of the histone genes in man. Cytogenet.
Cell Genet. 22: 359-363, 1978.

30. Tanguay, R. M.; Berube, D.; Gagne, R.: Localization of histone
genes to chromosomes 6, 12, and 1 by in situ hybridization. (Abstract) Cytogenet.
Cell Genet. 46: 702 only, 1987.

31. Tripputi, P.; Emanuel, B. S.; Croce, C. M.; Green, L. G.; Stein,
G. S.; Stein, J. L.: Human histone genes map to multiple chromosomes. Proc.
Nat. Acad. Sci. 83: 3185-3188, 1986.

32. Wang, H.; Huang, Z.-Q.; Xia, L.; Feng, Q.; Erdjument-Bromage,
H.; Strahl, B. D.; Briggs, S. D.; Allis, C. D.; Wong, J.; Tempst,
P.; Zhang, Y.: Methylation of histone H4 at arginine 3 facilitating
transcriptional activation by nuclear hormone receptor. Science 293:
853-857, 2001.

33. 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.

34. Yunis, J. J.; Chandler, M. E.: Localization of histone genes
to bands 7q32-36 in man and the homologous chromosome segments in
chimpanzee, gorilla, and orangutan. (Abstract) Cytogenet. Cell Genet. 25:
220 only, 1979.

*FIELD* CN
Ada Hamosh - updated: 10/14/2013
Matthew B. Gross - updated: 2/7/2013
Ada Hamosh - updated: 12/21/2012
Ada Hamosh - updated: 10/6/2010
Ada Hamosh - updated: 4/14/2010
Ada Hamosh - updated: 8/14/2009
Ada Hamosh - updated: 3/25/2008
Ada Hamosh - updated: 4/18/2006
Ada Hamosh - updated: 8/27/2001

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
alopez: 10/14/2013
alopez: 6/24/2013
mgross: 2/7/2013
mgross: 2/4/2013
alopez: 12/21/2012
alopez: 10/6/2010
mgross: 7/22/2010
alopez: 4/14/2010
wwang: 9/1/2009
alopez: 8/17/2009
terry: 8/14/2009
alopez: 3/25/2008
alopez: 4/24/2006
terry: 4/18/2006
tkritzer: 3/31/2003
alopez: 8/31/2001
terry: 8/27/2001
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602823
*RECORD*
*FIELD* NO
602823
*FIELD* TI
*602823 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER D; HIST1H4D
;;HISTONE GENE CLUSTER 1, H4D;;
read moreHIST1 CLUSTER, H4D;;
H4 HISTONE FAMILY, MEMBER B; H4FB;;
H4/B
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4D genes. All mouse and human H4 genes, including
HIST1H4D, encode the same protein.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes, including H4/b.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4D.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 4/3/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602824
*RECORD*
*FIELD* NO
602824
*FIELD* TI
*602824 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER F; HIST1H4F
;;HISTONE GENE CLUSTER 1, H4F;;
read moreHIST1 CLUSTER, H4F;;
H4 HISTONE FAMILY, MEMBER C; H4FC;;
H4/C
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

Albig et al. (1991) identified a gene encoding a member of the H4 class
of histones. Albig and Doenecke (1997) designated this gene H4/c.

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4F genes. All mouse and human H4 genes, including
HIST1H4F, encode the same protein.

MAPPING

By analysis of a YAC contig, Albig et al. (1997) mapped the H4/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 histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4F.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*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: 02/07/2013
Ada Hamosh - updated: 10/4/2004
Stylianos E. Antonarakis - updated: 11/26/2002

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 2/4/2013
mgross: 7/22/2010
wwang: 4/27/2009
alopez: 10/4/2004
tkritzer: 3/31/2003
mgross: 11/26/2002
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602825
*RECORD*
*FIELD* NO
602825
*FIELD* TI
*602825 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER K; HIST1H4K
;;HISTONE GENE CLUSTER 1, H4K;;
read moreHIST1 CLUSTER, H4K;;
H4 HISTONE FAMILY, MEMBER D; H4FD;;
H4/D
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4K genes. All mouse and human H4 genes, including
HIST1H4K, encode the same protein.

MAPPING

By analysis of a YAC contig from 6p22-p21.3, Albig and Doenecke (1997)
characterized a second cluster of 16 histone genes, including H4/d,
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 histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4K.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602826
*RECORD*
*FIELD* NO
602826
*FIELD* TI
*602826 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER J; HIST1H4J
;;HISTONE GENE CLUSTER 1, H4J;;
read moreHIST1 CLUSTER, H4J;;
H4 HISTONE FAMILY, MEMBER E; H4FE;;
H4/E
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

Heintz et al. (1981) cloned a gene, called H4/e, encoding an H4 histone.

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4J genes. All mouse and human H4 genes, including
HIST1H4J, encode the same protein.

MAPPING

By analysis of a YAC contig from 6p22-p21.3, Albig and Doenecke (1997)
characterized a second cluster of 16 histone genes, including H4/e,
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 histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4J.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

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

2. Heintz, N.; Zernik, M.; Roeder, R. G.: The structure of the human
histone genes: clustered but not tandemly repeated. Cell 24: 661-668,
1981.

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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602827
*RECORD*
*FIELD* NO
602827
*FIELD* TI
*602827 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER C; HIST1H4C
;;HISTONE GENE CLUSTER 1, H4C;;
read moreHIST1 CLUSTER, H4C;;
H4 HISTONE FAMILY, MEMBER G; H4FG;;
H4/G
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4C genes. All mouse and human H4 genes, including
HIST1H4C, encode the same protein.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes, including H4/g.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4C.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602828
*RECORD*
*FIELD* NO
602828
*FIELD* TI
*602828 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER H; HIST1H4H
;;HISTONE GENE CLUSTER 1, H4H;;
read moreHIST1 CLUSTER, H4H;;
H4 HISTONE FAMILY, MEMBER H; H4FH;;
H4/H
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4H genes. All mouse and human H4 genes, including
HIST1H4H, encode the same protein.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes, including H4/h.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4H.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602829
*RECORD*
*FIELD* NO
602829
*FIELD* TI
*602829 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER B; HIST1H4B
;;HISTONE GENE CLUSTER 1, H4B;;
read moreHIST1 CLUSTER, H4B;;
H4 HISTONE FAMILY, MEMBER I; H4FI;;
H4/I
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4B genes. All mouse and human H4 genes, including
HIST1H4B, encode the same protein.

MAPPING

By analysis of a YAC contig from 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes, including H4/i.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4B.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602830
*RECORD*
*FIELD* NO
602830
*FIELD* TI
*602830 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER E; HIST1H4E
;;HISTONE GENE CLUSTER 1, H4E;;
read moreHIST1 CLUSTER, H4E;;
H4 HISTONE FAMILY, MEMBER J; H4FJ; H4/J
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

By genomic sequence analysis, Marzluff et al. (2002) identified the
human HIST1H4E gene. All H4 genes, including HIST1H4E, encode the same
protein.

MAPPING

By analysis of a YAC contig from chromosome 6p21.3, Albig et al. (1997)
characterized a cluster of 35 histone genes, including H4/j.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4E.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602831
*RECORD*
*FIELD* NO
602831
*FIELD* TI
*602831 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER L; HIST1H4L
;;HISTONE GENE CLUSTER 1, H4L;;
read moreHIST1 CLUSTER, H4L;;
H4 HISTONE FAMILY, MEMBER K; H4FK;;
H4/K
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

Albig et al. (1997) identified a gene, designated H4/k, encoding a
member of the H4 class of histones.

By genomic sequence analysis, Marzluff et al. (2002) identified the
human HIST1H4L gene. All H4 genes, including HIST1H4L, encode the same
protein.

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 H4/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 histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4L.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
alopez: 8/26/1998
alopez: 7/14/1998
alopez: 7/10/1998

MIM 602833
*RECORD*
*FIELD* NO
602833
*FIELD* TI
*602833 HISTONE GENE CLUSTER 1, H4 HISTONE FAMILY, MEMBER I; HIST1H4I
;;HISTONE GENE CLUSTER 1, H4I;;
read moreHIST1 CLUSTER, H4I;;
H4 HISTONE FAMILY, MEMBER M; H4FM; H4M
H4FM/BCL6 FUSION GENE, INCLUDED
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

By cloning the junctional area of a recurring translocation,
t(3;6)(q27;p21), in B cell-type non-Hodgkin lymphoma, Akasaka et al.
(1997) identified a gene encoding a member of the H4 class of histones.
Albig and Doenecke (1997) designated this gene H4/m.

By genomic sequence analysis, Marzluff et al. (2002) identified the
mouse and human HIST1H4I genes. All mouse and human H4 genes, including
HIST1H4I, encode the same protein.

MAPPING

By FISH, Akasaka et al. (1997) mapped the H4/m gene to chromosome
6p21.3, within the cluster of histone genes in this region.

By genomic sequence analysis, Marzluff et al. (2002) determined that the
histone gene cluster on chromosome 6p22-p21, which they called histone
gene cluster-1 (HIST1), contains 55 histone genes, including HIST1H4I.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

CYTOGENETICS

In 2 cases of patients carrying the t(3;6)(q27;p21) translocation,
Akasaka et al. (1997) found that the H4/m gene was substituted for the
5-prime regulatory elements of BCL6 (109565) and fused with coding exons
3-9 of BCL6 in the same transcriptional orientation. Since H4 gene
expression is tightly coupled to DNA replication, these authors
suggested that the translocation causes inappropriate expression of BCL6
during the cell cycle, leading to the development of non-Hodgkin
lymphoma.

*FIELD* RF
1. Akasaka, T.; Miura, I.; Takahashi, N.; Akasaka, H.; Yonetani, N.;
Ohno, H.; Fukuhara, S.; Okuma, M.: A recurring translocation, t(3;6)(q27;p21),
in non-Hodgkin's lymphoma results in replacement of the 5-prime regulatory
region of BCL6 with a novel H4 histone gene. Cancer Res. 57: 7-12,
1997.

2. Albig, W.; Doenecke, D.: The human histone gene cluster at the
D6S105 locus. Hum. Genet. 101: 284-294, 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: 02/07/2013

*FIELD* CD
Rebekah S. Rasooly: 7/10/1998

*FIELD* ED
mgross: 02/07/2013
mgross: 7/22/2010
tkritzer: 3/31/2003
tkritzer: 3/18/2003
alopez: 9/8/1998
alopez: 8/26/1998
alopez: 7/10/1998

MIM 615069
*RECORD*
*FIELD* NO
615069
*FIELD* TI
*615069 HISTONE GENE CLUSTER 4, H4 HISTONE; HIST4H4
;;HISTONE GENE CLUSTER 4, H4;;
read moreHIST4 CLUSTER, H4;;
H4/P
*FIELD* TX
For background information on histones, histone gene clusters, and the
H4 histone family, see HIST1H4A (602822).

CLONING

Using PCR, Marzluff et al. (2002) cloned human HIST4H4. All mouse and
human H4 genes, including HIST4H4, encode the same protein. The HIST4H4
mRNA ends in a conserved stem loop found in replication-dependent
histones. An S1 nuclease protection assay showed that HIST4H4 was
expressed in human U2OS and 293T cell lines.

MAPPING

By genomic sequence analysis, Marzluff et al. (2002) mapped the HIST4H4
gene to chromosome 12p13.1. They mapped the mouse ortholog to a syntenic
region on chromosome 6G1.

GENE FUNCTION

See HIST1H4A (602822) for functional information on H4 histones.

*FIELD* RF
1. 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* CD
Matthew B. Gross: 2/7/2013

*FIELD* ED
mgross: 02/07/2013