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{{PBB|geneid=2146}}
'''组蛋白-離氨酸''N''-甲基转移酶EZH2'''是一个由人类''EZH2''[[基因]]所编码的[[酶]]<ref name="pmid8954776">{{cite journal | author = Chen H, Rossier C, Antonarakis SE | title = Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2 | journal = Genomics | volume = 38 | issue = 1 | pages = 30–7 |date=Mar 1997 | pmid = 8954776 | pmc = | doi = 10.1006/geno.1996.0588 }}</ref><ref name="pmid17172412">{{cite journal | author = Fiskus W, Pranpat M, Balasis M, Herger B, Rao R, Chinnaiyan A, Atadja P, Bhalla K | title = Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells | journal = Mol Cancer Ther | volume = 5 | issue = 12 | pages = 3096–104 |date=Dec 2006 | pmid = 17172412 | pmc = | doi = 10.1158/1535-7163.MCT-06-0418 }}</ref>，化学式为：C3710H5822O1160N1076S47<ref>{{Cite web |title=Expasy - ProtParam |url=https://web.expasy.org/cgi-bin/protparam/protparam_bis.cgi?Q15910@1-746@ |website=web.expasy.org |access-date=2026-02-09}}</ref>。已鉴定该基因转录出的两种转录物变异体编码不同的亚型<ref name="entrez">{{cite web| title = Entrez Gene: EZH2 enhancer of zeste homolog 2 (Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2146| accessdate = | archive-date = 2019-10-16| archive-url = https://web.archive.org/web/20191016120752/https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2146| dead-url = no}}</ref>。

== 功能 ==
该基因编码的蛋白属于[[多梳家族蛋白|多梳家族]]（PcG）成员。PcG家族成员相互结合形成多聚蛋白复合物，这种复合物涉及到在细胞世代间维持基因的转录抑制状态。EZH2主要通过将三个[[甲基]]基团加到[[组蛋白3]]的27号[[赖氨酸]]（H3K27）上行使基因沉默者的角色，三甲基化H3K27是维持[[染色质]]凝聚的一种重要修饰<ref name="pmid12351676">{{cite journal | author = Ru Cao, Liangjun Wang, Hengbin Wang, Li Xia, Hediye Erdjument-Bromage, Paul Tempst, Richard S Jones, Yi Zhang| title = Role of histone H3 lysine 27 methylation in Polycomb-group silencing | url = https://archive.org/details/sim_science_2002-11-01_298_5595/page/1038| journal = Science | volume = 298 | issue = 5595 | pages = 1039–43 |date=NOV 2002 | pmid = 12351676 | pmc = | doi = 10.1126/science.1076997 }}</ref>。

该蛋白与胚胎[[外胚层]]发育蛋白（[[EED]]）、癌蛋白[[VAV1]]和X连锁核蛋白（[[ATRX|XNP]]）之间关系密切。EZH2蛋白可能在造血系统和中枢神经系统中起到重要作用<ref name="entrez" />。

== 临床意义 ==
''EZH2''基因中的突变导致[[韦弗综合征]]<ref name="pmid22177091">{{cite journal | author = Gibson WT, Hood RL, Zhan SH, Bulman DE, Fejes AP, Moore R, Mungall AJ, Eydoux P, Babul-Hirji R, An J, Marra MA, Chitayat D, Boycott KM, Weaver DD, Jones SJ | title = Mutations in EZH2 Cause Weaver Syndrome | journal = Am J Hum Genet | volume = 90| issue = 1| pages = 110–8|date=December 2011 | pmid = 22177091 | doi = 10.1016/j.ajhg.2011.11.018 }}</ref>。[[mir-101微RNA前体家族|miR-101]]在正常情况下阻止编码EZH2的mRNA进入翻译阶段。因此这一微RNA的基因一旦缺失就会导致产生过量的EZH2<ref name="pmid21321380">{{cite journal | author = Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, de Witt Hamer PC, Marquez VE, Cloos J, Krichevsky AM, Noske DP, Tannous BA, Würdinger T | title = miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis | journal = Oncotarget | volume = 1 | issue = 8 | pages = 710–20 |date=December 2010 | pmid = 21321380 | pmc = 3124376 | doi = }}</ref>。EZH2过多表达可能导致癌症形成，这是因为过多地[[组蛋白甲基化]][[抑癌基因]]将导致其表达沉默。一种靶向EZH2药物的临床前模型显示其能够抑制脑癌及前列腺癌的进展<ref name="pmid19934320">{{cite journal | author = Suvà ML, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle JC, Baumer K, Le Bitoux MA, Marino D, Cironi L, Marquez VE, Clément V, Stamenkovic I | title = EZH2 is essential for glioblastoma cancer stem cell maintenance | url = https://archive.org/details/sim_cancer-research_2009-12-15_69_24/page/9210 | journal = Cancer Res. | volume = 69 | issue = 24 | pages = 9211–8 |date=December 2009 | pmid = 19934320 | doi = 10.1158/0008-5472.CAN-09-1622 }}</ref><ref name="pmid21501485">{{cite journal | author = Crea F, Hurt EM, Mathews LA, Cabarcas SM, Sun L, Marquez VE, Danesi R, Farrar WL | title = Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer | journal = Mol. Cancer | volume = 10 | issue = | pages = 40 | year = 2011 | pmid = 21501485 | pmc = 3100246 | doi = 10.1186/1476-4598-10-40 }}</ref>。

== 相互作用 ==
EZH2与下列蛋白质有着[[蛋白質交互作用]]：[[ATRX]]<ref name="pmid9499421">{{cite journal | author = Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L | title = Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein | journal = Hum. Mol. Genet. | volume = 7 | issue = 4 | pages = 679–84 |date=April 1998 | pmid = 9499421 | doi = 10.1093/hmg/7.4.679 }}</ref>、[[EED]]<ref name="pmid9584197">{{cite journal | author = van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E | title = Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes | url = https://archive.org/details/sim_molecular-and-cellular-biology_1998-06_18_6/page/3572 | journal = Mol. Cell. Biol. | volume = 18 | issue = 6 | pages = 3572–9 |date=June 1998 | pmid = 9584197 | pmc = 108938 | doi = }}</ref><ref name="pmid9742080">{{cite journal | author = Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K | title = Point mutations in the WD40 domain of Eed block its interaction with Ezh2 | url = https://archive.org/details/sim_molecular-and-cellular-biology_1998-10_18_10/page/5634 | journal = Mol. Cell. Biol. | volume = 18 | issue = 10 | pages = 5634–42 |date=October 1998 | pmid = 9742080 | pmc = 109149 | doi = }}</ref>、[[HDAC1]]<ref name="pmid10581039">{{cite journal | author = van der Vlag J, Otte AP | title = Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation | journal = Nat. Genet. | volume = 23 | issue = 4 | pages = 474–8 |date=December 1999 | pmid = 10581039 | doi = 10.1038/70602 }}</ref>、[[HDAC2]]<ref name=PMID 10581039 />和[[VAV1]]<ref name="pmid8649418">{{cite journal | author = Hobert O, Jallal B, Ullrich A | title = Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression | journal = Mol. Cell. Biol. | volume = 16 | issue = 6 | pages = 3066–73 |date=June 1996 | pmid = 8649418 | pmc = 231301 | doi = | url =https://archive.org/details/sim_molecular-and-cellular-biology_1996-06_16_6/page/3066}}</ref>。
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== 参考文献 ==
{{reflist|35em}}

== 深入阅读 ==
{{refbegin|35em}}
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*{{cite journal | author=De Haan G, Gerrits A |title=Epigenetic control of hematopoietic stem cell aging the case of Ezh2. |journal=Ann. N. Y. Acad. Sci. |volume=1106 |issue= 1|pages= 233–9 |year= 2007 |pmid= 17332078 |doi= 10.1196/annals.1392.008 }}
*{{cite journal | author=Hobert O, Jallal B, Ullrich A |title=Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression. | url=https://archive.org/details/sim_molecular-and-cellular-biology_1996-06_16_6/page/3066 |journal=Mol. Cell. Biol. |volume=16 |issue= 6 |pages= 3066–73 |year= 1996 |pmid= 8649418 |doi= | pmc=231301 }}
*{{cite journal | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791–806 |year= 1997 |pmid= 8889548 |doi=10.1101/gr.6.9.791 }}
*{{cite journal | author=Abel KJ, Brody LC, Valdes JM, ''et al.'' |title=Characterization of [[EZH1]], a human homolog of Drosophila Enhancer of zeste near BRCA1. |journal=Genomics |volume=37 |issue= 2 |pages= 161–71 |year= 1997 |pmid= 8921387 |doi= 10.1006/geno.1996.0537 }}
*{{cite journal | author=Laible G, Wolf A, Dorn R, ''et al.'' |title=Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres. | url=https://archive.org/details/sim_embo-journal_1997-06-02_16_11/page/3218 |journal=EMBO J. |volume=16 |issue= 11 |pages= 3219–32 |year= 1997 |pmid= 9214638 |doi= 10.1093/emboj/16.11.3219 | pmc=1169939 }}
*{{cite journal | author=Cardoso C, Timsit S, Villard L, ''et al.'' |title=Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein. |journal=Hum. Mol. Genet. |volume=7 |issue= 4 |pages= 679–84 |year= 1998 |pmid= 9499421 |doi=10.1093/hmg/7.4.679 }}
*{{cite journal | author=van Lohuizen M, Tijms M, Voncken JW, ''et al.'' |title=Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes. | url=https://archive.org/details/sim_molecular-and-cellular-biology_1998-06_18_6/page/3572 |journal=Mol. Cell. Biol. |volume=18 |issue= 6 |pages= 3572–9 |year= 1998 |pmid= 9584197 |doi= | pmc=108938 }}
*{{cite journal | author=Sewalt RG, van der Vlag J, Gunster MJ, ''et al.'' |title=Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes. | url=https://archive.org/details/sim_molecular-and-cellular-biology_1998-06_18_6/page/3586 |journal=Mol. Cell. Biol. |volume=18 |issue= 6 |pages= 3586–95 |year= 1998 |pmid= 9584199 |doi= | pmc=108940 }}
*{{cite journal | author=Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K |title=Point mutations in the WD40 domain of Eed block its interaction with Ezh2. | url=https://archive.org/details/sim_molecular-and-cellular-biology_1998-10_18_10/page/5634 |journal=Mol. Cell. Biol. |volume=18 |issue= 10 |pages= 5634–42 |year= 1998 |pmid= 9742080 |doi= | pmc=109149 }}
*{{cite journal | author=van der Vlag J, Otte AP |title=Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. |journal=Nat. Genet. |volume=23 |issue= 4 |pages= 474–8 |year= 1999 |pmid= 10581039 |doi= 10.1038/70602 }}
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*{{cite journal | author=Raaphorst FM, Otte AP, van Kemenade FJ, ''et al.'' |title=Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation. | url=https://archive.org/details/sim_journal-of-immunology_2001-05-15_166_10/page/5924 |journal=J. Immunol. |volume=166 |issue= 10 |pages= 5925–34 |year= 2001 |pmid= 11342607 |doi= }}
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*{{cite journal | author=Varambally S, Dhanasekaran SM, Zhou M, ''et al.'' |title=The polycomb group protein EZH2 is involved in progression of prostate cancer. | url=https://archive.org/details/sim_nature-uk_2002-10-10_419_6907/page/624 |journal=Nature |volume=419 |issue= 6907 |pages= 624–9 |year= 2002 |pmid= 12374981 |doi= 10.1038/nature01075 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
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*{{cite journal | author=Hillier LW, Fulton RS, Fulton LA, ''et al.'' |title=The DNA sequence of human chromosome 7. | url=https://archive.org/details/sim_nature-uk_2003-07-10_424_6945/page/156 |journal=Nature |volume=424 |issue= 6945 |pages= 157–64 |year= 2003 |pmid= 12853948 |doi= 10.1038/nature01782 }}
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[[Category:EC 2.1.1]]

EZH2 - 版本历史

2026年2月9日 (一) 05:19 imported>曦城星月