The Polycomb group protein EZH2 directly controls DNA methylation
The Polycomb group protein EZH2 directly controls DNA methylation
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DOI：
10.1038/nature04431
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发表时间：
2006-02-16
期刊：
影响因子：
64.8
通讯作者：
Fuks, F
中科院分区：
文献类型：
--
作者：
Viré, E;Brenner, C;Fuks, F
表观遗传基因沉默的建立和维持是细胞决定和功能的基础（1）。参与基因活性遗传抑制的基本表观遗传系统是Polycomb组（PcG）蛋白（2，3）和DNA甲基化（4，5）系统。在这里，我们表明，相应的沉默途径是机械连接。我们发现PcG蛋白EZH 2（Zeste同源物2的增强子）在Polycomb阻遏复合物2和3（PRC 2/3）的背景下与DNA甲基转移酶（DNMT）相互作用，并与体内DNMT活性相关。染色质免疫沉淀表明，DNMT与几个EZH 2抑制基因的结合取决于EZH 2的存在。此外，我们通过亚硫酸氢盐基因组测序表明，EZH 2是EZH 2靶启动子DNA甲基化所必需的。我们的研究结果表明，EZH 2作为DNA甲基转移酶的招募平台，从而突出了两个关键的表观遗传抑制系统之间以前未被认识到的直接联系。
The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function(1). The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins(2,3) and the DNA methylation(4,5) systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 ( Enhancer of Zeste homolog 2) interacts within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3) - with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicate that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, we show by bisulphite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems.