PRC2 directly methylates GATA4 and represses its transcriptional activity
PRC2 directly methylates GATA4 and represses its transcriptional activity
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PRC2 直接甲基化 GATA4 并抑制其转录活性。
DOI：
10.1101/gad.173930.111
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发表时间：
2012-01-01
影响因子：
10.5
通讯作者：
Pu, William T.
中科院分区：
文献类型：
--
作者：
He, Aibin;Shen, Xiaohua;Pu, William T.
多梳抑制复合物2（PRC2）通过沉积三甲基化组蛋白H3 Lys 27（H3K27me3）表观遗传标记来沉默异位基因表达程序，从而促进组织特异性分化。在这里，我们表明，EZH2，PRC2的催化亚基，是心脏形态发生所需的。在体外和胎儿心脏中，EZH2与心脏转录因子GATA4相互作用，并直接甲基化它在赖氨酸299。GATA4的PRC2甲基化通过减少其与p300的相互作用和由p300引起的乙酰化而减弱其转录活性。我们的研究结果揭示了PRC2介导的转录抑制的新机制，其中PRC2甲基化转录因子以抑制其转录活性。
Polycomb-repressive complex 2 (PRC2) promotes tissue-specific differentiation by depositing trimethylated histone H3 Lys 27 (H3K27me3) epigenetic marks to silence ectopic gene expression programs. Here, we show that EZH2, the catalytic subunit of PRC2, is required for cardiac morphogenesis. Both in vitro and in fetal hearts, EZH2 interacted with cardiac transcription factor GATA4 and directly methylated it at Lys 299. PRC2 methylation of GATA4 attenuated its transcriptional activity by reducing its interaction with and acetylation by p300. Our results reveal a new mechanism of PRC2-mediated transcriptional repression in which PRC2 methylates a transcription factor to inhibit its transcriptional activity.