EZH2

zeste同源物2增强子（果蝇属）
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	4MI0
标识
代号	EZH2; ENX-1; ENX1; EZH1; KMT6; KMT6A; WVS2
扩展标识	遗传学：601573 鼠基因：107940 同源基因：37926 GeneCards: EZH2 Gene
EC編號	2.1.1.43
基因本体论描述
分子功能	· core promoter binding; · DNA binding; · chromatin binding; · protein binding; · histone-lysine N-methyltransferase activity; · histone methyltransferase activity; · sequence-specific DNA binding;
细胞成分	· ESC/E(Z) complex; · pronucleus;
生物过程	· S phase of mitotic cell cycle; · negative regulation of transcription from RNA polymerase II promoter; · chromatin organization; · transcription, DNA-dependent; · regulation of transcription, DNA-dependent; · positive regulation of epithelial to mesenchymal transition; · regulation of gliogenesis; · cerebellar cortex development; · positive regulation of Ras GTPase activity; · negative regulation of transcription elongation from RNA polymerase II promoter; · regulation of cell proliferation; · positive regulation of MAP kinase activity; · negative regulation of epidermal cell differentiation; · negative regulation of gene expression, epigenetic; · negative regulation of transcription, DNA-dependent; · negative regulation of retinoic acid receptor signaling pathway; · negative regulation of striated muscle cell differentiation; · G1 to G0 transition; · histone H3-K27 methylation; · positive regulation of protein serine/threonine kinase activity;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体

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[1][2]。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[3]。

功能

该基因编码的蛋白属于多梳家族（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[4]。

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（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[3]。

临床意义

EZH2基因中的突变导致韦弗综合征[5]。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[6]。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[7][8]。

相互作用

EZH2与下列蛋白质有着蛋白質交互作用：ATRX[9]、EED[10][11]、HDAC1[12]、HDAC2[13]和VAV1[14]。

参考文献

Chen H, Rossier C, Antonarakis SE. . Genomics. Mar 1997, 38 (1): 30–7. PMID 8954776. doi:10.1006/geno.1996.0588.
Fiskus W, Pranpat M, Balasis M, Herger B, Rao R, Chinnaiyan A, Atadja P, Bhalla K. . Mol Cancer Ther. Dec 2006, 5 (12): 3096–104. PMID 17172412. doi:10.1158/1535-7163.MCT-06-0418.
. （原始内容存档于2019-10-16）.
Ru Cao, Liangjun Wang, Hengbin Wang, Li Xia, Hediye Erdjument-Bromage, Paul Tempst, Richard S Jones, Yi Zhang. . Science. NOV 2002, 298 (5595): 1039–43. PMID 12351676. doi:10.1126/science.1076997. 请检查|date=中的日期值 (帮助)
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. . Am J Hum Genet. December 2011, 90 (1): 110–8. PMID 22177091. doi:10.1016/j.ajhg.2011.11.018.
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. . Oncotarget. December 2010, 1 (8): 710–20. PMC 3124376 . PMID 21321380.
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. . Cancer Res. December 2009, 69 (24): 9211–8. PMID 19934320. doi:10.1158/0008-5472.CAN-09-1622.
Crea F, Hurt EM, Mathews LA, Cabarcas SM, Sun L, Marquez VE, Danesi R, Farrar WL. . Mol. Cancer. 2011, 10: 40. PMC 3100246 . PMID 21501485. doi:10.1186/1476-4598-10-40.
Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L. . Hum. Mol. Genet. April 1998, 7 (4): 679–84. PMID 9499421. doi:10.1093/hmg/7.4.679.
van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E. . Mol. Cell. Biol. June 1998, 18 (6): 3572–9. PMC 108938 . PMID 9584197.
Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. . Mol. Cell. Biol. October 1998, 18 (10): 5634–42. PMC 109149 . PMID 9742080.
van der Vlag J, Otte AP. . Nat. Genet. December 1999, 23 (4): 474–8. PMID 10581039. doi:10.1038/70602.
Hobert O, Jallal B, Ullrich A. . Mol. Cell. Biol. June 1996, 16 (6): 3066–73. PMC 231301 . PMID 8649418.

深入阅读

Zeidler M, Kleer CG. . J. Mol. Histol. 2007, 37 (5-7): 219–23. PMID 16855786. doi:10.1007/s10735-006-9042-9.
De Haan G, Gerrits A. . Ann. N. Y. Acad. Sci. 2007, 1106 (1): 233–9. PMID 17332078. doi:10.1196/annals.1392.008.
Hobert O, Jallal B, Ullrich A. . Mol. Cell. Biol. 1996, 16 (6): 3066–73. PMC 231301 . PMID 8649418.
Bonaldo MF, Lennon G, Soares MB. . Genome Res. 1997, 6 (9): 791–806. PMID 8889548. doi:10.1101/gr.6.9.791.
Abel KJ, Brody LC, Valdes JM; et al. . Genomics. 1997, 37 (2): 161–71. PMID 8921387. doi:10.1006/geno.1996.0537.
Laible G, Wolf A, Dorn R; et al. . EMBO J. 1997, 16 (11): 3219–32. PMC 1169939 . PMID 9214638. doi:10.1093/emboj/16.11.3219.
Cardoso C, Timsit S, Villard L; et al. . Hum. Mol. Genet. 1998, 7 (4): 679–84. PMID 9499421. doi:10.1093/hmg/7.4.679.
van Lohuizen M, Tijms M, Voncken JW; et al. . Mol. Cell. Biol. 1998, 18 (6): 3572–9. PMC 108938 . PMID 9584197.
Sewalt RG, van der Vlag J, Gunster MJ; et al. . Mol. Cell. Biol. 1998, 18 (6): 3586–95. PMC 108940 . PMID 9584199.
Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. . Mol. Cell. Biol. 1998, 18 (10): 5634–42. PMC 109149 . PMID 9742080.
van der Vlag J, Otte AP. . Nat. Genet. 1999, 23 (4): 474–8. PMID 10581039. doi:10.1038/70602.
Cardoso C, Mignon C, Hetet G; et al. . Eur. J. Hum. Genet. 2000, 8 (3): 174–80. PMID 10780782. doi:10.1038/sj.ejhg.5200439.
Raaphorst FM, Otte AP, van Kemenade FJ; et al. . J. Immunol. 2001, 166 (10): 5925–34. PMID 11342607.
O'Connell S, Wang L, Robert S; et al. . J. Biol. Chem. 2001, 276 (46): 43065–73. PMID 11571280. doi:10.1074/jbc.M104294200.
Varambally S, Dhanasekaran SM, Zhou M; et al. . Nature. 2002, 419 (6907): 624–9. PMID 12374981. doi:10.1038/nature01075.
Strausberg RL, Feingold EA, Grouse LH; et al. . Proc. Natl. Acad. Sci. U.S.A. 2003, 99 (26): 16899–903. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
Scherer SW, Cheung J, MacDonald JR; et al. . Science. 2003, 300 (5620): 767–72. PMC 2882961 . PMID 12690205. doi:10.1126/science.1083423.
Hillier LW, Fulton RS, Fulton LA; et al. . Nature. 2003, 424 (6945): 157–64. PMID 12853948. doi:10.1038/nature01782.
Kleer CG, Cao Q, Varambally S; et al. . Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (20): 11606–11. PMC 208805 . PMID 14500907. doi:10.1073/pnas.1933744100.

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[pmid8954776-1] Chen H, Rossier C, Antonarakis SE. . Genomics. Mar 1997, 38 (1): 30–7. PMID 8954776. doi:10.1006/geno.1996.0588.

[pmid17172412-2] Fiskus W, Pranpat M, Balasis M, Herger B, Rao R, Chinnaiyan A, Atadja P, Bhalla K. . Mol Cancer Ther. Dec 2006, 5 (12): 3096–104. PMID 17172412. doi:10.1158/1535-7163.MCT-06-0418.

[entrez-3] . （原始内容存档于2019-10-16）.

[pmid12351676-4] Ru Cao, Liangjun Wang, Hengbin Wang, Li Xia, Hediye Erdjument-Bromage, Paul Tempst, Richard S Jones, Yi Zhang. . Science. NOV 2002, 298 (5595): 1039–43. PMID 12351676. doi:10.1126/science.1076997. 请检查|date=中的日期值 (帮助)

[pmid22177091-5] 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. . Am J Hum Genet. December 2011, 90 (1): 110–8. PMID 22177091. doi:10.1016/j.ajhg.2011.11.018.

[pmid21321380-6] 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. . Oncotarget. December 2010, 1 (8): 710–20. PMC 3124376 . PMID 21321380.

[pmid19934320-7] 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. . Cancer Res. December 2009, 69 (24): 9211–8. PMID 19934320. doi:10.1158/0008-5472.CAN-09-1622.

[pmid21501485-8] Crea F, Hurt EM, Mathews LA, Cabarcas SM, Sun L, Marquez VE, Danesi R, Farrar WL. . Mol. Cancer. 2011, 10: 40. PMC 3100246 . PMID 21501485. doi:10.1186/1476-4598-10-40.

[pmid9499421-9] Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L. . Hum. Mol. Genet. April 1998, 7 (4): 679–84. PMID 9499421. doi:10.1093/hmg/7.4.679.

[pmid9584197-10] van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E. . Mol. Cell. Biol. June 1998, 18 (6): 3572–9. PMC 108938 . PMID 9584197.

[pmid9742080-11] Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. . Mol. Cell. Biol. October 1998, 18 (10): 5634–42. PMC 109149 . PMID 9742080.

[pmid10581039-12] van der Vlag J, Otte AP. . Nat. Genet. December 1999, 23 (4): 474–8. PMID 10581039. doi:10.1038/70602.

[pmid8649418-14] Hobert O, Jallal B, Ullrich A. . Mol. Cell. Biol. June 1996, 16 (6): 3066–73. PMC 231301 . PMID 8649418.