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PMID: 22215809 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

PRC2 directly methylates GATA4 and represses its transcriptional activity.

Genes & development ·Vol. 26 ·No. 1 ·2012-01-01 ·Pages 37-42

He A, Shen X, Ma Q, Cao J, von Gise A, Zhou P, Wang G, Marquez VE, Orkin SH, Pu WT

Abstract

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.

MeSH Terms
Animals E1A-Associated p300 Protein/metabolism Enhancer of Zeste Homolog 2 Protein GATA4 Transcription Factor/genetics,metabolism Gene Expression Regulation, Developmental Histone-Lysine N-Methyltransferase/metabolism Methylation Mice Polycomb Repressive Complex 2 Polycomb-Group Proteins Protein Binding Repressor Proteins/metabolism
Chemicals
GATA4 Transcription Factor Gata4 protein, mouse Polycomb-Group Proteins Repressor Proteins Enhancer of Zeste Homolog 2 Protein Ezh2 protein, mouse Histone-Lysine N-Methyltransferase Polycomb Repressive Complex 2 E1A-Associated p300 Protein Ep300 protein, mouse
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
He Aibin
Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Shen Xiaohua
Ma Qing
Cao Jingjing
von Gise Alexander
Zhou Pingzhu
Wang Gang
Marquez Victor E
Orkin Stuart H
Pu William T
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.173930.111
Published
2012-01-01
Pages
37-42
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC3258964
Subset
IM
Grants
NHLBI NIH HHS · R01HL095712 · United States
Intramural NIH HHS · United States
NHLBI NIH HHS · U01HL098166 · United States
NHLBI NIH HHS · R01 HL095712 · United States
NHLBI NIH HHS · U01 HL098166 · United States
External Links
PubMed source DOI: 10.1101/gad.173930.111 PMC Full Text View journal details
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