PRC2 directly methylates GATA4 and represses its transcriptional activity
- Aibin He1,2,
- Xiaohua Shen2,3,6,
- Qing Ma1,2,
- Jingjing Cao1,2,
- Alexander von Gise1,2,
- Pingzhu Zhou1,2,
- Gang Wang1,2,
- Victor E. Marquez4,
- Stuart H. Orkin2,3,5 and
- William T. Pu1,2,7
- 1Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 2Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA;
- 3Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 4Chemical Biology Laboratory, Center for Cancer Research, NCI-Frederick, Frederick, Maryland 21702, USA;
- 5Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
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.
Keywords
Footnotes
-
↵7 Corresponding author.
E-mail wpu{at}enders.tch.harvard.edu.
-
Supplemental material is available for this article.
-
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.173930.111.
- Received July 7, 2011.
- Accepted November 23, 2011.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press