PRC2 directly methylates GATA4 and represses its transcriptional activity

被引：225

作者：

He, Aibin ^{[1
,2
]}

Shen, Xiaohua ^{[2
,3
]}

Ma, Qing ^{[1
,2
]}

Cao, Jingjing ^{[1
,2
]}

von Gise, Alexander ^{[1
,2
]}

Zhou, Pingzhu ^{[1
,2
]}

Wang, Gang ^{[1
,2
]}

Marquez, Victor E. ^{[4
]}

Orkin, Stuart H. ^{[2
,3
,5
]}

Pu, William T. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Dept Cardiol, Childrens Hosp Boston, Boston, MA 02115 USA

[2] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[3] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Childrens Hosp Boston, Boston, MA 02115 USA

[4] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA

[5] Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

GENES & DEVELOPMENT | 2012年 / 26卷 / 01期

基金：

美国国家卫生研究院;

关键词：

epigenetics; heart development; polycomb complex; transcriptional regulation; HISTONE METHYLTRANSFERASE ACTIVITY; H3; LYSINE-27; METHYLATION; STEM-CELLS; POLYCOMB; EZH2; DIFFERENTIATION; ACETYLATION; PROTEIN; GENOME; HEART;

D O I：

10.1101/gad.173930.111

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：37 / 42

页数：6

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