Conway Eric, Healy Evan, Bracken Adrian P
Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
Curr Opin Cell Biol. 2015 Dec;37:42-8. doi: 10.1016/j.ceb.2015.10.003. Epub 2015 Nov 11.
The Polycomb Repressive Complex 2 (PRC2) is a multiprotein chromatin modifying complex that is essential for vertebrate development and differentiation. It is composed of a trimeric core of SUZ12, EED and EZH1/2 and is responsible for catalysing both di-methylation and tri-methylation of Histone H3 at lysine 27 (H3K27me2/3). Both H3K27 methylations contribute to the role of PRC2 in maintaining cellular identity. In all cell types, the H3K27me3 modification is associated with repression of genes encoding regulators of alternative lineages. The less well-characterised H3K27me2 modification is ubiquitous throughout the genome and is thought to act like a protective blanket to maintain the repression of non-H3K27me3 associated genes and cell-type-specific enhancers of alternative lineages. Recent cancer genome sequencing studies highlighted that several genes encoding PRC2 components as well as Histone H3 are mutated in multiple cancer types. Intriguingly, these cancers have changes in the global levels of the H3K27me2 and H3K27me3 modifications as well as genome-wide redistributions. Exciting new studies suggest that these changes confer context dependent blocks in cellular differentiation and increased vulnerability to aberrant cancer signalling pathways.
多梳抑制复合物2（PRC2）是一种多蛋白染色质修饰复合物，对脊椎动物的发育和分化至关重要。它由SUZ12、EED和EZH1/2的三聚体核心组成，负责催化组蛋白H3赖氨酸27位的二甲基化和三甲基化（H3K27me2/3）。这两种H3K27甲基化都有助于PRC2在维持细胞特性方面发挥作用。在所有细胞类型中，H3K27me3修饰与编码替代谱系调节因子的基因的抑制相关。特征较少的H3K27me2修饰在整个基因组中普遍存在，被认为起到保护作用，以维持与非H3K27me3相关基因和替代谱系的细胞类型特异性增强子的抑制。最近的癌症基因组测序研究表明，多个癌症类型中编码PRC2组分以及组蛋白H3的几个基因发生了突变。有趣的是，这些癌症在H3K27me2和H3K27me3修饰的整体水平以及全基因组重新分布方面都有变化。令人兴奋的新研究表明，这些变化在细胞分化中赋予了依赖于背景的阻滞作用，并增加了对异常癌症信号通路的易感性。
