The Histone H3 Lysine 9 Methyltransferases G9a and GLP Regulate Polycomb Repressive Complex 2-Mediated Gene Silencing
The Histone H3 Lysine 9 Methyltransferases G9a and GLP Regulate Polycomb Repressive Complex 2-Mediated Gene Silencing
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DOI：
10.1016/j.molcel.2013.12.005
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发表时间：
2014-01-23
期刊：
影响因子：
16
通讯作者：
Ait-Si-Ali, Slimane
中科院分区：
文献类型：
--
作者：
Mozzetta, Chiara;Pontis, Julien;Ait-Si-Ali, Slimane
G9a/GLP和Polycomb抑制复合体2(PRC2)是两种主要的表观遗传沉默机制，尤其是赖氨酸9和27(H3K9和H3K27)上的组蛋白H3甲基化。尽管H3K9和H3K27甲基化之间存在串扰的证据已经开始出现，但它们实际的相互作用仍然难以捉摸。在这里，我们证明了PRC2和G9a/GLP在物理和功能上相互作用。此外，结合不同的全基因组方法，我们证明了Ezh2和G9a/GLP共享许多重要的共同基因组靶点，编码发育和神经元调节。此外，我们还证明了G9a的酶活性调节了PRC2基因组对其目标基因的子集的招募。综上所述，我们的发现显示了两个主要的组蛋白赖氨酸甲基化机制之间出乎意料的相互作用，这两个机制共同维持了对发育基因子集的沉默。
G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes.