The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
Biol Chem. 2020 Jul 28;401(8):933-943. doi: 10.1515/hsz-2019-0436.
The polycomb repressive complex 2 (PRC2) consists of three core components EZH2, SUZ12 and EED. EZH2 catalyzes the methylation of lysine 27 of histone H3, a modification associated with gene silencing. Through gene duplication higher vertebrate genomes also encode a second partially redundant methyltransferase, EZH1. Within the mammalian immune system most research has concentrated on EZH2 which is expressed predominantly in proliferating cells. EZH2 and other PRC2 components are required for hematopoietic stem cell function and lymphocyte development, at least in part by repressing cell cycle inhibitors. At later stages of immune cell differentiation, EZH2 plays essential roles in humoral and cell-mediated adaptive immunity, as well as the maintenance of immune homeostasis. EZH2 is often overactive in cancers, through both gain-of-function mutations and over-expression, an observation that has led to the development and clinical testing of specific EZH2 inhibitors. Such inhibitors may also be of use in inflammatory and autoimmune settings, as EZH2 inhibition dampens the immune response. Here, we will review the current state of understanding of the roles for EZH2, and PRC2 more generally, in the development and function of the immune system.
多梳抑制复合物 2（PRC2）由三个核心成分 EZH2、SUZ12 和 EED 组成。EZH2 催化组蛋白 H3 赖氨酸 27 的甲基化，这种修饰与基因沉默有关。通过基因复制，高等脊椎动物基因组还编码了第二种部分冗余的甲基转移酶 EZH1。在哺乳动物免疫系统中，大多数研究都集中在 EZH2 上，EZH2 主要在增殖细胞中表达。EZH2 和其他 PRC2 成分对于造血干细胞功能和淋巴细胞发育是必需的，至少部分是通过抑制细胞周期抑制剂。在免疫细胞分化的后期阶段，EZH2 在体液和细胞介导的适应性免疫中发挥重要作用，以及维持免疫稳态。EZH2 在癌症中常常过度活跃，这既是由于功能获得性突变，也是由于过度表达，这一观察结果导致了特定的 EZH2 抑制剂的开发和临床测试。EZH2 抑制可以抑制免疫反应，因此这类抑制剂在炎症和自身免疫性疾病中也可能有用。在这里，我们将回顾目前对 EZH2 以及更普遍的 PRC2 在免疫系统发育和功能中的作用的理解。
