Full text data of H2AFZ
H2AFZ
(H2AZ)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Histone H2A.Z; H2A/z
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Histone H2A.Z; H2A/z
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P0C0S5
ID H2AZ_HUMAN Reviewed; 128 AA.
AC P0C0S5; B2RD56; P17317; Q6I9U0;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 88.
DE RecName: Full=Histone H2A.Z;
DE Short=H2A/z;
GN Name=H2AFZ; Synonyms=H2AZ;
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 [MRNA].
RC TISSUE=Brain;
RX PubMed=3344202; DOI=10.1093/nar/16.3.1113;
RA Hatch C.L., Bonner W.M.;
RT "Sequence of cDNAs for mammalian H2A.Z, an evolutionarily diverged but
RT highly conserved basal histone H2A isoprotein species.";
RL Nucleic Acids Res. 16:1113-1124(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1697587;
RA Hatch C.L., Bonner W.M.;
RT "The human histone H2A.Z gene. Sequence and regulation.";
RL J. Biol. Chem. 265:15211-15218(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Skeletal muscle, and 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 [8]
RP UBIQUITINATION AT LYS-122.
RX PubMed=11835281; DOI=10.1002/bies.10038;
RA Jason L.J.M., Moore S.C., Lewis J.D., Lindsey G., Ausio J.;
RT "Histone ubiquitination: a tagging tail unfolds?";
RL Bioessays 24:166-174(2002).
RN [9]
RP FUNCTION.
RX PubMed=15878876; DOI=10.1074/jbc.M501784200;
RA Farris S.D., Rubio E.D., Moon J.J., Gombert W.M., Nelson B.H.,
RA Krumm A.;
RT "Transcription-induced chromatin remodeling at the c-myc gene involves
RT the local exchange of histone H2A.Z.";
RL J. Biol. Chem. 280:25298-25303(2005).
RN [10]
RP MASS SPECTROMETRY.
RX PubMed=16457589; DOI=10.1021/pr050269n;
RA Boyne M.T. II, Pesavento J.J., Mizzen C.A., Kelleher N.L.;
RT "Precise characterization of human histones in the H2A gene family by
RT top down mass spectrometry.";
RL J. Proteome Res. 5:248-253(2006).
RN [11]
RP ACETYLATION AT LYS-5; LYS-8 AND LYS-12, 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-5 AND LYS-8, AND MASS
RP SPECTROMETRY.
RX PubMed=16319397; DOI=10.1074/mcp.M500288-MCP200;
RA Bonenfant D., Coulot M., Towbin H., Schindler P., van Oostrum J.;
RT "Characterization of histones H2A and H2B variants and their post-
RT translational modifications by mass spectrometry.";
RL Mol. Cell. Proteomics 5:541-552(2006).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2; LYS-8; LYS-12 AND LYS-14,
RP MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
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 [14]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH THE NUCLEOSOME.
RX PubMed=11101893; DOI=10.1038/81971;
RA Suto R.K., Clarkson M.J., Tremethick D.J., Luger K.;
RT "Crystal structure of a nucleosome core particle containing the
RT variant histone H2A.Z.";
RL Nat. Struct. Biol. 7:1121-1124(2000).
CC -!- FUNCTION: Variant histone H2A which replaces conventional H2A in a
CC subset of nucleosomes. Nucleosomes wrap and compact DNA into
CC chromatin, limiting DNA accessibility to the cellular machineries
CC which require DNA as a template. Histones thereby play a central
CC role in transcription regulation, DNA repair, DNA replication and
CC chromosomal stability. DNA accessibility is regulated via a
CC complex set of post-translational modifications of histones, also
CC called histone code, and nucleosome remodeling. May be involved in
CC the formation of constitutive heterochromatin. May be required for
CC chromosome segregation during cell division.
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. H2A or its variant H2AFZ forms a
CC heterodimer with H2B. H2AFZ interacts with INCENP (By similarity).
CC -!- INTERACTION:
CC O43257:ZNHIT1; NbExp=3; IntAct=EBI-1199859, EBI-347522;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC -!- PTM: Monoubiquitination of Lys-122 gives a specific tag for
CC epigenetic transcriptional repression.
CC -!- PTM: Acetylated on Lys-5, Lys-8 and Lys-12 during interphase.
CC Acetylation disappears at mitosis (By similarity).
CC -!- PTM: Not phosphorylated (By similarity).
CC -!- MASS SPECTROMETRY: Mass=13413.4; Method=Electrospray; Range=2-128;
CC Note=Monoisotopic, not modified; Source=PubMed:16457589;
CC -!- SIMILARITY: Belongs to the histone H2A family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X52317; CAA36553.1; -; mRNA.
DR EMBL; M37583; AAA35984.1; -; mRNA.
DR EMBL; L10138; AAC61625.1; -; Genomic_DNA.
DR EMBL; CR457415; CAG33696.1; -; mRNA.
DR EMBL; AK315413; BAG37803.1; -; mRNA.
DR EMBL; AC097460; AAY41013.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX06118.1; -; Genomic_DNA.
DR EMBL; BC018002; AAH18002.1; -; mRNA.
DR EMBL; BC020936; AAH20936.1; -; mRNA.
DR EMBL; BC103743; AAI03744.1; -; mRNA.
DR PIR; A35881; A35881.
DR RefSeq; NP_002097.1; NM_002106.3.
DR UniGene; Hs.119192; -.
DR PDB; 1F66; X-ray; 2.60 A; C/G=1-128.
DR PDBsum; 1F66; -.
DR ProteinModelPortal; P0C0S5; -.
DR SMR; P0C0S5; 17-123.
DR DIP; DIP-38593N; -.
DR IntAct; P0C0S5; 4.
DR MINT; MINT-1605675; -.
DR STRING; 9606.ENSP00000296417; -.
DR PhosphoSite; P0C0S5; -.
DR DMDM; 83288408; -.
DR PaxDb; P0C0S5; -.
DR PRIDE; P0C0S5; -.
DR DNASU; 3015; -.
DR Ensembl; ENST00000296417; ENSP00000296417; ENSG00000164032.
DR GeneID; 3015; -.
DR KEGG; hsa:3015; -.
DR UCSC; uc003hvo.1; human.
DR CTD; 3015; -.
DR GeneCards; GC04M100869; -.
DR HGNC; HGNC:4741; H2AFZ.
DR HPA; CAB022549; -.
DR HPA; HPA045242; -.
DR MIM; 142763; gene.
DR neXtProt; NX_P0C0S5; -.
DR PharmGKB; PA29119; -.
DR eggNOG; COG5262; -.
DR HOGENOM; HOG000234652; -.
DR HOVERGEN; HBG009342; -.
DR InParanoid; P0C0S5; -.
DR KO; K11251; -.
DR OMA; IHRYLMN; -.
DR OrthoDB; EOG7M0NTR; -.
DR PhylomeDB; P0C0S5; -.
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 ChiTaRS; H2AFZ; human.
DR EvolutionaryTrace; P0C0S5; -.
DR GeneWiki; H2AFZ; -.
DR GenomeRNAi; 3015; -.
DR NextBio; 11952; -.
DR PMAP-CutDB; P0C0S5; -.
DR PRO; PR:P0C0S5; -.
DR Bgee; P0C0S5; -.
DR CleanEx; HS_H2AFZ; -.
DR Genevestigator; P0C0S5; -.
DR GO; GO:0000786; C:nucleosome; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006334; P:nucleosome assembly; IEA:InterPro.
DR Gene3D; 1.10.20.10; -; 1.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR007125; Histone_core_D.
DR InterPro; IPR002119; Histone_H2A.
DR Pfam; PF00125; Histone; 1.
DR PRINTS; PR00620; HISTONEH2A.
DR SMART; SM00414; H2A; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR PROSITE; PS00046; HISTONE_H2A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosome; Complete proteome; DNA-binding;
KW Isopeptide bond; Nucleosome core; Nucleus; Reference proteome;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 128 Histone H2A.Z.
FT /FTId=PRO_0000055297.
FT REGION 2 17 Required for interaction with INCENP (By
FT similarity).
FT REGION 93 103 Required for interaction with INCENP (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 5 5 N6-acetyllysine.
FT MOD_RES 8 8 N6-acetyllysine.
FT MOD_RES 12 12 N6-acetyllysine.
FT MOD_RES 14 14 N6-acetyllysine.
FT CROSSLNK 122 122 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT HELIX 20 24
FT HELIX 30 39
FT HELIX 51 75
FT TURN 76 78
FT STRAND 80 82
FT HELIX 84 93
FT HELIX 95 100
FT STRAND 103 105
FT HELIX 116 118
SQ SEQUENCE 128 AA; 13553 MW; E024E53818230371 CRC64;
MAGGKAGKDS GKAKTKAVSR SQRAGLQFPV GRIHRHLKSR TTSHGRVGAT AAVYSAAILE
YLTAEVLELA GNASKDLKVK RITPRHLQLA IRGDEELDSL IKATIAGGGV IPHIHKSLIG
KKGQQKTV
//
ID H2AZ_HUMAN Reviewed; 128 AA.
AC P0C0S5; B2RD56; P17317; Q6I9U0;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 88.
DE RecName: Full=Histone H2A.Z;
DE Short=H2A/z;
GN Name=H2AFZ; Synonyms=H2AZ;
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 [MRNA].
RC TISSUE=Brain;
RX PubMed=3344202; DOI=10.1093/nar/16.3.1113;
RA Hatch C.L., Bonner W.M.;
RT "Sequence of cDNAs for mammalian H2A.Z, an evolutionarily diverged but
RT highly conserved basal histone H2A isoprotein species.";
RL Nucleic Acids Res. 16:1113-1124(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1697587;
RA Hatch C.L., Bonner W.M.;
RT "The human histone H2A.Z gene. Sequence and regulation.";
RL J. Biol. Chem. 265:15211-15218(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Skeletal muscle, and 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 [8]
RP UBIQUITINATION AT LYS-122.
RX PubMed=11835281; DOI=10.1002/bies.10038;
RA Jason L.J.M., Moore S.C., Lewis J.D., Lindsey G., Ausio J.;
RT "Histone ubiquitination: a tagging tail unfolds?";
RL Bioessays 24:166-174(2002).
RN [9]
RP FUNCTION.
RX PubMed=15878876; DOI=10.1074/jbc.M501784200;
RA Farris S.D., Rubio E.D., Moon J.J., Gombert W.M., Nelson B.H.,
RA Krumm A.;
RT "Transcription-induced chromatin remodeling at the c-myc gene involves
RT the local exchange of histone H2A.Z.";
RL J. Biol. Chem. 280:25298-25303(2005).
RN [10]
RP MASS SPECTROMETRY.
RX PubMed=16457589; DOI=10.1021/pr050269n;
RA Boyne M.T. II, Pesavento J.J., Mizzen C.A., Kelleher N.L.;
RT "Precise characterization of human histones in the H2A gene family by
RT top down mass spectrometry.";
RL J. Proteome Res. 5:248-253(2006).
RN [11]
RP ACETYLATION AT LYS-5; LYS-8 AND LYS-12, 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-5 AND LYS-8, AND MASS
RP SPECTROMETRY.
RX PubMed=16319397; DOI=10.1074/mcp.M500288-MCP200;
RA Bonenfant D., Coulot M., Towbin H., Schindler P., van Oostrum J.;
RT "Characterization of histones H2A and H2B variants and their post-
RT translational modifications by mass spectrometry.";
RL Mol. Cell. Proteomics 5:541-552(2006).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2; LYS-8; LYS-12 AND LYS-14,
RP MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
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 [14]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH THE NUCLEOSOME.
RX PubMed=11101893; DOI=10.1038/81971;
RA Suto R.K., Clarkson M.J., Tremethick D.J., Luger K.;
RT "Crystal structure of a nucleosome core particle containing the
RT variant histone H2A.Z.";
RL Nat. Struct. Biol. 7:1121-1124(2000).
CC -!- FUNCTION: Variant histone H2A which replaces conventional H2A in a
CC subset of nucleosomes. Nucleosomes wrap and compact DNA into
CC chromatin, limiting DNA accessibility to the cellular machineries
CC which require DNA as a template. Histones thereby play a central
CC role in transcription regulation, DNA repair, DNA replication and
CC chromosomal stability. DNA accessibility is regulated via a
CC complex set of post-translational modifications of histones, also
CC called histone code, and nucleosome remodeling. May be involved in
CC the formation of constitutive heterochromatin. May be required for
CC chromosome segregation during cell division.
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. H2A or its variant H2AFZ forms a
CC heterodimer with H2B. H2AFZ interacts with INCENP (By similarity).
CC -!- INTERACTION:
CC O43257:ZNHIT1; NbExp=3; IntAct=EBI-1199859, EBI-347522;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC -!- PTM: Monoubiquitination of Lys-122 gives a specific tag for
CC epigenetic transcriptional repression.
CC -!- PTM: Acetylated on Lys-5, Lys-8 and Lys-12 during interphase.
CC Acetylation disappears at mitosis (By similarity).
CC -!- PTM: Not phosphorylated (By similarity).
CC -!- MASS SPECTROMETRY: Mass=13413.4; Method=Electrospray; Range=2-128;
CC Note=Monoisotopic, not modified; Source=PubMed:16457589;
CC -!- SIMILARITY: Belongs to the histone H2A family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X52317; CAA36553.1; -; mRNA.
DR EMBL; M37583; AAA35984.1; -; mRNA.
DR EMBL; L10138; AAC61625.1; -; Genomic_DNA.
DR EMBL; CR457415; CAG33696.1; -; mRNA.
DR EMBL; AK315413; BAG37803.1; -; mRNA.
DR EMBL; AC097460; AAY41013.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX06118.1; -; Genomic_DNA.
DR EMBL; BC018002; AAH18002.1; -; mRNA.
DR EMBL; BC020936; AAH20936.1; -; mRNA.
DR EMBL; BC103743; AAI03744.1; -; mRNA.
DR PIR; A35881; A35881.
DR RefSeq; NP_002097.1; NM_002106.3.
DR UniGene; Hs.119192; -.
DR PDB; 1F66; X-ray; 2.60 A; C/G=1-128.
DR PDBsum; 1F66; -.
DR ProteinModelPortal; P0C0S5; -.
DR SMR; P0C0S5; 17-123.
DR DIP; DIP-38593N; -.
DR IntAct; P0C0S5; 4.
DR MINT; MINT-1605675; -.
DR STRING; 9606.ENSP00000296417; -.
DR PhosphoSite; P0C0S5; -.
DR DMDM; 83288408; -.
DR PaxDb; P0C0S5; -.
DR PRIDE; P0C0S5; -.
DR DNASU; 3015; -.
DR Ensembl; ENST00000296417; ENSP00000296417; ENSG00000164032.
DR GeneID; 3015; -.
DR KEGG; hsa:3015; -.
DR UCSC; uc003hvo.1; human.
DR CTD; 3015; -.
DR GeneCards; GC04M100869; -.
DR HGNC; HGNC:4741; H2AFZ.
DR HPA; CAB022549; -.
DR HPA; HPA045242; -.
DR MIM; 142763; gene.
DR neXtProt; NX_P0C0S5; -.
DR PharmGKB; PA29119; -.
DR eggNOG; COG5262; -.
DR HOGENOM; HOG000234652; -.
DR HOVERGEN; HBG009342; -.
DR InParanoid; P0C0S5; -.
DR KO; K11251; -.
DR OMA; IHRYLMN; -.
DR OrthoDB; EOG7M0NTR; -.
DR PhylomeDB; P0C0S5; -.
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 ChiTaRS; H2AFZ; human.
DR EvolutionaryTrace; P0C0S5; -.
DR GeneWiki; H2AFZ; -.
DR GenomeRNAi; 3015; -.
DR NextBio; 11952; -.
DR PMAP-CutDB; P0C0S5; -.
DR PRO; PR:P0C0S5; -.
DR Bgee; P0C0S5; -.
DR CleanEx; HS_H2AFZ; -.
DR Genevestigator; P0C0S5; -.
DR GO; GO:0000786; C:nucleosome; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006334; P:nucleosome assembly; IEA:InterPro.
DR Gene3D; 1.10.20.10; -; 1.
DR InterPro; IPR009072; Histone-fold.
DR InterPro; IPR007125; Histone_core_D.
DR InterPro; IPR002119; Histone_H2A.
DR Pfam; PF00125; Histone; 1.
DR PRINTS; PR00620; HISTONEH2A.
DR SMART; SM00414; H2A; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
DR PROSITE; PS00046; HISTONE_H2A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosome; Complete proteome; DNA-binding;
KW Isopeptide bond; Nucleosome core; Nucleus; Reference proteome;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 128 Histone H2A.Z.
FT /FTId=PRO_0000055297.
FT REGION 2 17 Required for interaction with INCENP (By
FT similarity).
FT REGION 93 103 Required for interaction with INCENP (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 5 5 N6-acetyllysine.
FT MOD_RES 8 8 N6-acetyllysine.
FT MOD_RES 12 12 N6-acetyllysine.
FT MOD_RES 14 14 N6-acetyllysine.
FT CROSSLNK 122 122 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT HELIX 20 24
FT HELIX 30 39
FT HELIX 51 75
FT TURN 76 78
FT STRAND 80 82
FT HELIX 84 93
FT HELIX 95 100
FT STRAND 103 105
FT HELIX 116 118
SQ SEQUENCE 128 AA; 13553 MW; E024E53818230371 CRC64;
MAGGKAGKDS GKAKTKAVSR SQRAGLQFPV GRIHRHLKSR TTSHGRVGAT AAVYSAAILE
YLTAEVLELA GNASKDLKVK RITPRHLQLA IRGDEELDSL IKATIAGGGV IPHIHKSLIG
KKGQQKTV
//
MIM
142763
*RECORD*
*FIELD* NO
142763
*FIELD* TI
*142763 H2A HISTONE FAMILY, MEMBER Z; H2AFZ
;;H2AZ HISTONE;;
H2AZ
*FIELD* TX
DESCRIPTION
read more
Histones wrap DNA to form nucleosome particles that compact eukaryotic
genomes. Each nucleosome core particle consists of DNA wrapped by an
octamer containing 2 molecules each of the highly conserved histones H2A
(see 613499), H2B (see 609904), H3 (see 602810), and H4 (see 602822). H1
histones (see 142709) occupy the linker DNA between nucleosomes.
Canonical histone genes are clustered in repeat arrays and their
transcription is tightly coupled to DNA replication. In contrast,
noncanonical variant histone genes are found singly in the genome, are
constitutively expressed, and encode histones that differ in primary
amino acid sequence from their canonical paralogs. Unlike canonical
histones that function primarily in genome packaging and gene
regulation, variant histones have roles in DNA repair, meiotic
recombination, chromosome segregation, transcription initiation and
termination, sex chromosome condensation, and sperm chromatin packaging.
H2AFZ is variant histone of the H2A family (review by Talbert and
Henikoff, 2010).
H2AZ is required for normal gene expression, is distributed throughout
the genome, and appears to be required for proper recruitment of RNA
polymerase II (see 180660) and TATA-binding protein (TBP; 600075) (Wong
et al., 2007).
For additional background information on histones, histone gene
clusters, and the H2A histone family, see HIST1H2AA (613499).
CLONING
Hatch and Bonner (1990) cloned and sequenced the human H2AZ gene.
Popescu et al. (1994) noted that a comparison of H2A amino acid
sequences showed that the H2AZ protein contains regions of low homology
with other H2A protein species alternating with regions of high
homology. The H2AZ gene contains introns and encodes a polyadenylated
mRNA species in contrast to the replication-linked histone genes that
lack introns and encode short mRNA species that terminate in a stem-loop
structure.
GENE FUNCTION
The conserved histone variant H2AZ has an important role in the
regulation of gene expression (Redon et al., 2002) and the establishment
of a buffer to the spread of silent heterochromatin (Meneghini et al.,
2003). Mizuguchi et al. (2004) found that in S. cerevisiae Swr1, a
Swi2/Snf2-related ATPase, is the catalytic core of a multisubunit,
histone variant exchanger that efficiently replaces the conventional
histone H2A with histone H2AZ in nucleosome arrays. Swr1 is required for
the deposition of histone H2AZ at specific chromosome locations in vivo,
and Swr1 and H2AZ commonly regulate a subset of yeast genes.
By chromatin immunoprecipitation analysis of a human lung carcinoma cell
line, Wong et al. (2007) found that SRCAP, the human ortholog of Swr1,
was recruited to both active and inactive promoters, with highest levels
of SRCAP on the active SP1 (189906), G3BP (608431), and FAD synthetase
(FLAD1; 610595) promoters. The sites of SRCAP recruitment on these
promoters overlapped or occurred adjacent to the sites of deposition of
H2AZ and acetylated H2AZ. Knockdown of SRCAP expression resulted in
decreased deposition of H2AZ and acetylated H1AZ and decreased levels of
SP1, G3BP, and FAD synthetase mRNA. Wong et al. (2007) concluded that
SRCAP mediates in vivo deposition of H2AZ.
Jin et al. (2009) characterized the genomewide distribution of
nucleosome core particles containing H3.3 (H3F3A; 601128) and/or H2A.Z
in HeLa cells. They found that highly labile particles containing both
H3.3 and H2A.Z were enriched at active promoters, enhancers, and
insulator regions. Jin et al. (2009) suggested that unstable particles
containing both H3.3 and H2A.Z may serve as place holders that are
easily displaced by transcription factors.
He et al. (2010) performed genomewide mapping of nucleosomes marked with
dimethylated H3K4 (H3K4me2) in upstream androgen receptor (AR;
313700)-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.
Luk et al. (2010) found that replacement of the 2 H2A-H2B dimers in
nucleosomes with 2 H2AZ-H2B dimers was stepwise and unidirectional in S.
cerevisiae. ATP hydrolysis by the SWR1 complex was specifically
activated by H2A-containing nucleosomes and additionally by H2AZ-H2B
dimers, leading to histone replacement.
H2A.Z deposition is controlled by SWR-C chromatin remodeling enzymes
that catalyze the nucleosomal exchange of canonical H2A with H2A with
H2A.Z. Watanabe et al. (2013) reported that acetylation of histone H3 on
lysine-56 (H3-K56Ac) alters the substrate specificity of SWR-C, leading
to promiscuous dimer exchange in which either H2A.Z or H2A can be
exchanged from nucleosomes. This result was confirmed in vivo, where
genomewide analysis demonstrated widespread decreases in H2A.Z levels in
yeast mutants with hyperacetylated H3K56. Watanabe et al. (2013)
concluded that a conserved SWR-C subunit may function as a 'lock' that
prevents removal of H2A.Z from nucleosomes.
GENE STRUCTURE
Hatch and Bonner (1990) determined that the H2AZ gene contains 5 exons.
MAPPING
Popescu et al. (1994) mapped the H2AZ gene to chromosome 4 by study of
human/hamster hybrid cell lines and regionalized the assignment to 4q24
by fluorescence in situ hybridization.
*FIELD* RF
1. Hatch, C. L.; Bonner, W. M.: The human histone H2A.Z gene. Sequence
and regulation. J. Biol. Chem. 265: 15211-15218, 1990.
2. He, H. H.; Meyer, C. A.; Shin, H.; Bailey, S. T.; Wei, G.; Wang,
Q.; Zhang, Y.; Xu, K.; Ni, M.; Lupien, M.; Mieczkowski, P.; Lieb,
J. D.; Zhao, K.; Brown, M.; Liu, S.: Nucleosome dynamics define transcriptional
enhancers. Nature Genet. 42: 343-347, 2010.
3. Jin, C.; Zang, C.; Wei, G.; Cui, K.; Peng, W.; Zhao, K.; Felsenfeld,
G.: H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free
regions' of active promoters and other regulatory regions. Nature
Genet. 41: 941-945, 2009.
4. Luk, E.; Ranjan, A.; FitzGerald, P. C.; Mizuguchi, G.; Huang, Y.;
Wei, D.; Wu, C.: Stepwise histone replacement by SWR1 requires dual
activation with histone H2A.Z and canonical nucleosome. Cell 143:
725-736, 2010.
5. Meneghini, M. D.; Wu, M.; Madhani, H. D.: Conserved histone variant
H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112:
725-736, 2003.
6. Mizuguchi, G.; Shen, X.; Landry, J.; Wu, W.-H.; Sen, S.; Wu, C.
: ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin
remodeling complex. Science 303: 343-348, 2004.
7. Popescu, N.; Zimonjic, D.; Hatch, C.; Bonner, W.: Chromosomal
mapping of the human histone gene H2AZ to 4q24 by fluorescence in
situ hybridization. Genomics 20: 333-335, 1994.
8. Redon, C.; Pilch, D.; Rogakou, E.; Sedelnikova, O.; Newrock, K.;
Bonner, W.: Histone H2A variants H2AX and H2AZ. Curr. Opin. Genet.
Dev. 12: 162-169, 2002.
9. Talbert, P. B.; Henikoff, S.: Histone variants--ancient wrap artists
of the epigenome. Nature Rev. Molec. Cell Biol. 11: 264-275, 2010.
10. Watanabe, S.; Radman-Livaja, M.; Rando, O. J.; Peterson, C. L.
: A histone acetylation switch regulates H2A.Z deposition by the SWR-C
remodeling enzyme. Science 340: 195-199, 2013.
11. Wong, M. M.; Cox, L. K.; Chrivia, J. C.: The chromatin remodeling
protein, SRCAP, is critical for deposition of the histone variant
H2A.Z at promoters. J. Biol. Chem. 282: 26132-26139, 2007.
*FIELD* CN
Ada Hamosh - updated: 05/06/2013
Matthew B. Gross - updated: 1/14/2013
Patricia A. Hartz - updated: 2/10/2011
Patricia A. Hartz - updated: 5/14/2010
Patricia A. Hartz - updated: 5/12/2010
Ada Hamosh - updated: 9/16/2009
Patricia A. Hartz - updated: 11/29/2007
Ada Hamosh - updated: 2/2/2004
Rebekah S. Rasooly - updated: 7/8/1998
*FIELD* CD
Victor A. McKusick: 4/6/1994
*FIELD* ED
alopez: 05/06/2013
mgross: 2/5/2013
mgross: 1/14/2013
mgross: 2/16/2011
terry: 2/10/2011
mgross: 5/17/2010
terry: 5/14/2010
terry: 5/12/2010
alopez: 9/22/2009
terry: 9/16/2009
mgross: 11/30/2007
terry: 11/29/2007
alopez: 2/2/2004
cwells: 1/14/2004
alopez: 8/26/1998
alopez: 7/8/1998
mark: 9/22/1996
carol: 4/6/1994
*RECORD*
*FIELD* NO
142763
*FIELD* TI
*142763 H2A HISTONE FAMILY, MEMBER Z; H2AFZ
;;H2AZ HISTONE;;
H2AZ
*FIELD* TX
DESCRIPTION
read more
Histones wrap DNA to form nucleosome particles that compact eukaryotic
genomes. Each nucleosome core particle consists of DNA wrapped by an
octamer containing 2 molecules each of the highly conserved histones H2A
(see 613499), H2B (see 609904), H3 (see 602810), and H4 (see 602822). H1
histones (see 142709) occupy the linker DNA between nucleosomes.
Canonical histone genes are clustered in repeat arrays and their
transcription is tightly coupled to DNA replication. In contrast,
noncanonical variant histone genes are found singly in the genome, are
constitutively expressed, and encode histones that differ in primary
amino acid sequence from their canonical paralogs. Unlike canonical
histones that function primarily in genome packaging and gene
regulation, variant histones have roles in DNA repair, meiotic
recombination, chromosome segregation, transcription initiation and
termination, sex chromosome condensation, and sperm chromatin packaging.
H2AFZ is variant histone of the H2A family (review by Talbert and
Henikoff, 2010).
H2AZ is required for normal gene expression, is distributed throughout
the genome, and appears to be required for proper recruitment of RNA
polymerase II (see 180660) and TATA-binding protein (TBP; 600075) (Wong
et al., 2007).
For additional background information on histones, histone gene
clusters, and the H2A histone family, see HIST1H2AA (613499).
CLONING
Hatch and Bonner (1990) cloned and sequenced the human H2AZ gene.
Popescu et al. (1994) noted that a comparison of H2A amino acid
sequences showed that the H2AZ protein contains regions of low homology
with other H2A protein species alternating with regions of high
homology. The H2AZ gene contains introns and encodes a polyadenylated
mRNA species in contrast to the replication-linked histone genes that
lack introns and encode short mRNA species that terminate in a stem-loop
structure.
GENE FUNCTION
The conserved histone variant H2AZ has an important role in the
regulation of gene expression (Redon et al., 2002) and the establishment
of a buffer to the spread of silent heterochromatin (Meneghini et al.,
2003). Mizuguchi et al. (2004) found that in S. cerevisiae Swr1, a
Swi2/Snf2-related ATPase, is the catalytic core of a multisubunit,
histone variant exchanger that efficiently replaces the conventional
histone H2A with histone H2AZ in nucleosome arrays. Swr1 is required for
the deposition of histone H2AZ at specific chromosome locations in vivo,
and Swr1 and H2AZ commonly regulate a subset of yeast genes.
By chromatin immunoprecipitation analysis of a human lung carcinoma cell
line, Wong et al. (2007) found that SRCAP, the human ortholog of Swr1,
was recruited to both active and inactive promoters, with highest levels
of SRCAP on the active SP1 (189906), G3BP (608431), and FAD synthetase
(FLAD1; 610595) promoters. The sites of SRCAP recruitment on these
promoters overlapped or occurred adjacent to the sites of deposition of
H2AZ and acetylated H2AZ. Knockdown of SRCAP expression resulted in
decreased deposition of H2AZ and acetylated H1AZ and decreased levels of
SP1, G3BP, and FAD synthetase mRNA. Wong et al. (2007) concluded that
SRCAP mediates in vivo deposition of H2AZ.
Jin et al. (2009) characterized the genomewide distribution of
nucleosome core particles containing H3.3 (H3F3A; 601128) and/or H2A.Z
in HeLa cells. They found that highly labile particles containing both
H3.3 and H2A.Z were enriched at active promoters, enhancers, and
insulator regions. Jin et al. (2009) suggested that unstable particles
containing both H3.3 and H2A.Z may serve as place holders that are
easily displaced by transcription factors.
He et al. (2010) performed genomewide mapping of nucleosomes marked with
dimethylated H3K4 (H3K4me2) in upstream androgen receptor (AR;
313700)-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.
Luk et al. (2010) found that replacement of the 2 H2A-H2B dimers in
nucleosomes with 2 H2AZ-H2B dimers was stepwise and unidirectional in S.
cerevisiae. ATP hydrolysis by the SWR1 complex was specifically
activated by H2A-containing nucleosomes and additionally by H2AZ-H2B
dimers, leading to histone replacement.
H2A.Z deposition is controlled by SWR-C chromatin remodeling enzymes
that catalyze the nucleosomal exchange of canonical H2A with H2A with
H2A.Z. Watanabe et al. (2013) reported that acetylation of histone H3 on
lysine-56 (H3-K56Ac) alters the substrate specificity of SWR-C, leading
to promiscuous dimer exchange in which either H2A.Z or H2A can be
exchanged from nucleosomes. This result was confirmed in vivo, where
genomewide analysis demonstrated widespread decreases in H2A.Z levels in
yeast mutants with hyperacetylated H3K56. Watanabe et al. (2013)
concluded that a conserved SWR-C subunit may function as a 'lock' that
prevents removal of H2A.Z from nucleosomes.
GENE STRUCTURE
Hatch and Bonner (1990) determined that the H2AZ gene contains 5 exons.
MAPPING
Popescu et al. (1994) mapped the H2AZ gene to chromosome 4 by study of
human/hamster hybrid cell lines and regionalized the assignment to 4q24
by fluorescence in situ hybridization.
*FIELD* RF
1. Hatch, C. L.; Bonner, W. M.: The human histone H2A.Z gene. Sequence
and regulation. J. Biol. Chem. 265: 15211-15218, 1990.
2. He, H. H.; Meyer, C. A.; Shin, H.; Bailey, S. T.; Wei, G.; Wang,
Q.; Zhang, Y.; Xu, K.; Ni, M.; Lupien, M.; Mieczkowski, P.; Lieb,
J. D.; Zhao, K.; Brown, M.; Liu, S.: Nucleosome dynamics define transcriptional
enhancers. Nature Genet. 42: 343-347, 2010.
3. Jin, C.; Zang, C.; Wei, G.; Cui, K.; Peng, W.; Zhao, K.; Felsenfeld,
G.: H3.3/H2A.Z double variant-containing nucleosomes mark 'nucleosome-free
regions' of active promoters and other regulatory regions. Nature
Genet. 41: 941-945, 2009.
4. Luk, E.; Ranjan, A.; FitzGerald, P. C.; Mizuguchi, G.; Huang, Y.;
Wei, D.; Wu, C.: Stepwise histone replacement by SWR1 requires dual
activation with histone H2A.Z and canonical nucleosome. Cell 143:
725-736, 2010.
5. Meneghini, M. D.; Wu, M.; Madhani, H. D.: Conserved histone variant
H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112:
725-736, 2003.
6. Mizuguchi, G.; Shen, X.; Landry, J.; Wu, W.-H.; Sen, S.; Wu, C.
: ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin
remodeling complex. Science 303: 343-348, 2004.
7. Popescu, N.; Zimonjic, D.; Hatch, C.; Bonner, W.: Chromosomal
mapping of the human histone gene H2AZ to 4q24 by fluorescence in
situ hybridization. Genomics 20: 333-335, 1994.
8. Redon, C.; Pilch, D.; Rogakou, E.; Sedelnikova, O.; Newrock, K.;
Bonner, W.: Histone H2A variants H2AX and H2AZ. Curr. Opin. Genet.
Dev. 12: 162-169, 2002.
9. Talbert, P. B.; Henikoff, S.: Histone variants--ancient wrap artists
of the epigenome. Nature Rev. Molec. Cell Biol. 11: 264-275, 2010.
10. Watanabe, S.; Radman-Livaja, M.; Rando, O. J.; Peterson, C. L.
: A histone acetylation switch regulates H2A.Z deposition by the SWR-C
remodeling enzyme. Science 340: 195-199, 2013.
11. Wong, M. M.; Cox, L. K.; Chrivia, J. C.: The chromatin remodeling
protein, SRCAP, is critical for deposition of the histone variant
H2A.Z at promoters. J. Biol. Chem. 282: 26132-26139, 2007.
*FIELD* CN
Ada Hamosh - updated: 05/06/2013
Matthew B. Gross - updated: 1/14/2013
Patricia A. Hartz - updated: 2/10/2011
Patricia A. Hartz - updated: 5/14/2010
Patricia A. Hartz - updated: 5/12/2010
Ada Hamosh - updated: 9/16/2009
Patricia A. Hartz - updated: 11/29/2007
Ada Hamosh - updated: 2/2/2004
Rebekah S. Rasooly - updated: 7/8/1998
*FIELD* CD
Victor A. McKusick: 4/6/1994
*FIELD* ED
alopez: 05/06/2013
mgross: 2/5/2013
mgross: 1/14/2013
mgross: 2/16/2011
terry: 2/10/2011
mgross: 5/17/2010
terry: 5/14/2010
terry: 5/12/2010
alopez: 9/22/2009
terry: 9/16/2009
mgross: 11/30/2007
terry: 11/29/2007
alopez: 2/2/2004
cwells: 1/14/2004
alopez: 8/26/1998
alopez: 7/8/1998
mark: 9/22/1996
carol: 4/6/1994