EZH2 Q15910

组蛋白-赖氨酸N-甲基转移酶EZH2 (EC 2.1.1.356) (ENX-1) (zeste同源物增强子2) (赖氨酸N-甲基转移酶6)

功能描述

PRC2/EED-EZH2复合物的催化亚基，该复合物是一种Polycomb group (PcG)复合物，能够甲基化组蛋白H3的'Lys-9' (H3K9me)和'Lys-27' (H3K27me)，导致受影响靶基因的转录抑制 (PubMed:14532106, PubMed:15225548, PubMed:15385962, PubMed:16618801, PubMed:16936726, PubMed:17344414, PubMed:22323599, PubMed:24474760, PubMed:26581166, PubMed:30026490, PubMed:30923826)。能够分别单甲基化、双甲基化和三甲基化组蛋白H3的'Lys-27'，形成H3K27me1、H3K27me2和H3K27me3 (PubMed:15231737, PubMed:17210787, PubMed:18285464, PubMed:22323599, PubMed:30923826)。对甲基化程度较低的底物表现出偏好，随着更多的甲基基团被整合到H3K27中，其活性逐渐丧失，活性顺序为H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599, PubMed:30923826)。与含EZH1的复合物相比，它在胚胎干细胞中更丰富，并在形成H3K27me3中起主要作用，这对于胚胎干细胞的特性和正确分化是必需的 (PubMed:19026781)。PRC2/EED-EZH2复合物也可能作为DNA甲基转移酶的招募平台，从而连接两个表观遗传抑制系统 (PubMed:16357870, PubMed:17200670)。被PRC2/EED-EZH2复合物抑制的基因包括HOXC8、HOXA9、MYT1、CDKN2A和视黄酸靶基因 (PubMed:16179254, PubMed:18086877, PubMed:20935635)。EZH2也可以甲基化非组蛋白，例如转录因子GATA4和核受体RORA (PubMed:23063525)。通过节律基因启动子处的组蛋白甲基化调节生物钟 (PubMed:16717091)。对于CRY1/2介导的抑制CLOCK-BMAL1异二聚体对PER1/2的转录激活至关重要；参与PER1/2启动子上组蛋白H3 'Lys-27'的双甲基化和三甲基化，这对CRY1/2蛋白抑制转录是必需的 (By similarity)。 {ECO:0000250|UniProtKB:Q61188, ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16179254, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:16717091, ECO:0000269|PubMed:16936726, ECO:0000269|PubMed:17200670, ECO:0000269|PubMed:17210787, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:22323599, ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:24474760, ECO:0000269|PubMed:26581166, ECO:0000269|PubMed:30026490, ECO:0000269|PubMed:30923826}。

组织特异性

In the ovary, expressed in primordial follicles and oocytes and also in external follicle cells (at protein level) (PubMed:31451685). Expressed in many tissues (PubMed:14532106). Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis (PubMed:14532106).

亚细胞定位

Nucleus