EZH2

zeste同源物2增強子（果蠅屬）
有效結構
PDB	直系同源檢索：PDBe, RCSB
PDB查詢代碼列表
	4MI0
標識
代號	EZH2; ENX-1; ENX1; EZH1; KMT6; KMT6A; WVS2
擴展標識	遺傳學：601573 鼠基因：107940 同源基因：37926 GeneCards: EZH2 Gene
EC編號	2.1.1.43
基因本體論描述
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;
細胞成分	· ESC/E(Z) complex; · pronucleus;
生物過程	· 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表達模式
	更多表達數據
直系同源體
	閱; 論; 編;

組蛋白-離氨酸N-甲基轉移酶EZH2是一個由人類EZH2基因所編碼的酶^[1]^[2]。已鑑定該基因轉錄出的兩種轉錄物變異體編碼不同的亞型^[3]。

功能[編輯]

該基因編碼的蛋白屬於多梳家族（PcG）成員。PcG家族成員相互結合形成多聚蛋白複合物，這種複合物涉及到在細胞世代間維持基因的轉錄抑制狀態。EZH2主要通過將三個甲基基團加到組蛋白3的27號賴氨酸（H3K27）上行使基因沉默者的角色，三甲基化H3K27是維持染色質凝聚的一種重要修飾^[4]。

該蛋白與胚胎外胚層發育蛋白（EED）、癌蛋白VAV1和X連鎖核蛋白（XNP）之間關係密切。EZH2蛋白可能在造血系統和中樞神經系統中起到重要作用^[3]。

臨床意義[編輯]

EZH2基因中的突變導致韋弗綜合徵^[5]。miR-101在正常情況下阻止編碼EZH2的mRNA進入翻譯階段。因此這一微RNA的基因一旦缺失就會導致產生過量的EZH2^[6]。EZH2過多表達可能導致癌症形成，這是因為過多地組蛋白甲基化抑癌基因將導致其表達沉默。一種靶向EZH2藥物的臨床前模型顯示其能夠抑制腦癌及前列腺癌的進展^[7]^[8]。

相互作用[編輯]

EZH2與下列蛋白質有着蛋白質交互作用：ATRX^[9]、EED^[10]^[11]、HDAC1^[12]、HDAC2引用錯誤：<ref>標籤有衝突或無效的屬性和VAV1^[13]。

參考文獻[編輯]

^ Chen H, Rossier C, Antonarakis SE. Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2. 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. Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells. Mol Cancer Ther. Dec 2006, 5 (12): 3096–104. PMID 17172412. doi:10.1158/1535-7163.MCT-06-0418.
^ ^3.0 ^3.1 Entrez Gene: EZH2 enhancer of zeste homolog 2 (Drosophila). （原始內容存檔於2019-10-16）.
^ Ru Cao, Liangjun Wang, Hengbin Wang, Li Xia, Hediye Erdjument-Bromage, Paul Tempst, Richard S Jones, Yi Zhang. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. NOV 2002, 298 (5595): 1039–43. PMID 12351676. doi:10.1126/science.1076997. 請檢查|date=中的日期值 (幫助)
^ 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. Mutations in EZH2 Cause Weaver Syndrome. 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. miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. 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. EZH2 is essential for glioblastoma cancer stem cell maintenance. 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. Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer. 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. Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein. 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. Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes. Mol. Cell. Biol. June 1998, 18 (6): 3572–9. PMC 108938 . PMID 9584197.
^ Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. Point mutations in the WD40 domain of Eed block its interaction with Ezh2. Mol. Cell. Biol. October 1998, 18 (10): 5634–42. PMC 109149 . PMID 9742080.
^ van der Vlag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat. Genet. December 1999, 23 (4): 474–8. PMID 10581039. doi:10.1038/70602.
^ Hobert O, Jallal B, Ullrich A. Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression. Mol. Cell. Biol. June 1996, 16 (6): 3066–73. PMC 231301 . PMID 8649418.

深入閱讀[編輯]

Zeidler M, Kleer CG. The Polycomb group protein Enhancer of Zeste 2: its links to DNA repair and breast cancer.. J. Mol. Histol. 2007, 37 (5-7): 219–23. PMID 16855786. doi:10.1007/s10735-006-9042-9.
De Haan G, Gerrits A. Epigenetic control of hematopoietic stem cell aging the case of Ezh2.. Ann. N. Y. Acad. Sci. 2007, 1106 (1): 233–9. PMID 17332078. doi:10.1196/annals.1392.008.
Hobert O, Jallal B, Ullrich A. Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression.. Mol. Cell. Biol. 1996, 16 (6): 3066–73. PMC 231301 . PMID 8649418.
Bonaldo MF, Lennon G, Soares MB. Normalization and subtraction: two approaches to facilitate gene discovery.. Genome Res. 1997, 6 (9): 791–806. PMID 8889548. doi:10.1101/gr.6.9.791.
Abel KJ, Brody LC, Valdes JM; et al. Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1.. Genomics. 1997, 37 (2): 161–71. PMID 8921387. doi:10.1006/geno.1996.0537.
Laible G, Wolf A, Dorn R; et al. Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres.. 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. Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein.. 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. Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes.. Mol. Cell. Biol. 1998, 18 (6): 3572–9. PMC 108938 . PMID 9584197.
Sewalt RG, van der Vlag J, Gunster MJ; et al. Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes.. Mol. Cell. Biol. 1998, 18 (6): 3586–95. PMC 108940 . PMID 9584199.
Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. Point mutations in the WD40 domain of Eed block its interaction with Ezh2.. Mol. Cell. Biol. 1998, 18 (10): 5634–42. PMC 109149 . PMID 9742080.
van der Vlag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation.. Nat. Genet. 1999, 23 (4): 474–8. PMID 10581039. doi:10.1038/70602.
Cardoso C, Mignon C, Hetet G; et al. The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders.. 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. Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation.. J. Immunol. 2001, 166 (10): 5925–34. PMID 11342607.
O'Connell S, Wang L, Robert S; et al. Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein.. J. Biol. Chem. 2001, 276 (46): 43065–73. PMID 11571280. doi:10.1074/jbc.M104294200.
Varambally S, Dhanasekaran SM, Zhou M; et al. The polycomb group protein EZH2 is involved in progression of prostate cancer.. Nature. 2002, 419 (6907): 624–9. PMID 12374981. doi:10.1038/nature01075.
Strausberg RL, Feingold EA, Grouse LH; et al. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.. 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. Human chromosome 7: DNA sequence and biology.. Science. 2003, 300 (5620): 767–72. PMC 2882961 . PMID 12690205. doi:10.1126/science.1083423.
Hillier LW, Fulton RS, Fulton LA; et al. The DNA sequence of human chromosome 7.. Nature. 2003, 424 (6945): 157–64. PMID 12853948. doi:10.1038/nature01782.
Kleer CG, Cao Q, Varambally S; et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells.. Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (20): 11606–11. PMC 208805 . PMID 14500907. doi:10.1073/pnas.1933744100.

[pmid8954776-1] Chen H, Rossier C, Antonarakis SE. Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2. 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. Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells. Mol Cancer Ther. Dec 2006, 5 (12): 3096–104. PMID 17172412. doi:10.1158/1535-7163.MCT-06-0418.

[entrez-3] 3.0 ^3.1 Entrez Gene: EZH2 enhancer of zeste homolog 2 (Drosophila). （原始內容存檔於2019-10-16）.

[pmid12351676-4] Ru Cao, Liangjun Wang, Hengbin Wang, Li Xia, Hediye Erdjument-Bromage, Paul Tempst, Richard S Jones, Yi Zhang. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. NOV 2002, 298 (5595): 1039–43. PMID 12351676. doi:10.1126/science.1076997. 請檢查|date=中的日期值 (幫助)

[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. Mutations in EZH2 Cause Weaver Syndrome. 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. miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. 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. EZH2 is essential for glioblastoma cancer stem cell maintenance. 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. Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer. 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. Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein. 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. Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes. Mol. Cell. Biol. June 1998, 18 (6): 3572–9. PMC 108938 . PMID 9584197.

[pmid9742080-11] Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K. Point mutations in the WD40 domain of Eed block its interaction with Ezh2. Mol. Cell. Biol. October 1998, 18 (10): 5634–42. PMC 109149 . PMID 9742080.

[pmid10581039-12] van der Vlag J, Otte AP. Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat. Genet. December 1999, 23 (4): 474–8. PMID 10581039. doi:10.1038/70602.

[pmid8649418-13] Hobert O, Jallal B, Ullrich A. Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression. Mol. Cell. Biol. June 1996, 16 (6): 3066–73. PMC 231301 . PMID 8649418.

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