PRC2 directly methylates GATA4 and represses its transcriptional activity

被引：220
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
收藏
页码：37 / 42
页数：6
相关论文
共 34 条
  • [1] High-resolution profiling of histone methylations in the human genome
    Barski, Artern
    Cuddapah, Suresh
    Cui, Kairong
    Roh, Tae-Young
    Schones, Dustin E.
    Wang, Zhibin
    Wei, Gang
    Chepelev, Iouri
    Zhao, Keji
    [J]. CELL, 2007, 129 (04) : 823 - 837
  • [2] Regulation of activity of the transcription factor GATA-1 by acetylation
    Boyes, J
    Byfield, P
    Nakatani, Y
    Ogryzko, V
    [J]. NATURE, 1998, 396 (6711) : 594 - 598
  • [3] Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions
    Bracken, AP
    Dietrich, N
    Pasini, D
    Hansen, KH
    Helin, K
    [J]. GENES & DEVELOPMENT, 2006, 20 (09) : 1123 - 1136
  • [4] Role of histone H3 lysine 27 methylation in polycomb-group silencing
    Cao, R
    Wang, LJ
    Wang, HB
    Xia, L
    Erdjument-Bromage, H
    Tempst, P
    Jones, RS
    Zhang, Y
    [J]. SCIENCE, 2002, 298 (5595) : 1039 - 1043
  • [5] HL-1 cells: A cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte
    Claycomb, WC
    Lanson, NA
    Stallworth, BS
    Egeland, DB
    Delcarpio, JB
    Bahinski, A
    Izzo, NJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (06) : 2979 - 2984
  • [6] p300 functions as a coactivator of transcription factor GATA-4
    Dai, YS
    Markham, BE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (40) : 37178 - 37185
  • [7] A generic tool for biotinylation of tagged proteins in transgenic mice
    Driegen, S
    Ferreira, R
    van Zon, A
    Strouboulis, J
    Jaegle, M
    Grosveld, F
    Philipsen, S
    Meijer, D
    [J]. TRANSGENIC RESEARCH, 2005, 14 (04) : 477 - 482
  • [8] The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors
    Durocher, D
    Charron, F
    Schwartz, RJ
    Warren, R
    Nemer, M
    [J]. EMBO JOURNAL, 1997, 16 (18) : 5687 - 5696
  • [9] Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells
    Ezhkova, Elena
    Pasolli, H. Amalia
    Parker, Joel S.
    Stokes, Nicole
    Su, I-hsin
    Hannon, Gregory
    Tarakhovsky, Alexander
    Fuchs, Elaine
    [J]. CELL, 2009, 136 (06) : 1122 - 1135
  • [10] Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells
    Fiskus, Warren
    Wang, Yongchao
    Sreekumar, Arun
    Buckley, Kathleen M.
    Shi, Huidong
    Jillella, Anand
    Ustun, Celalettin
    Rao, Rekha
    Fernandez, Pravina
    Chen, Jianguang
    Balusu, Ramesh
    Koul, Sanjay
    Atadja, Peter
    Marquez, Victor E.
    Bhalla, Kapil N.
    [J]. BLOOD, 2009, 114 (13) : 2733 - 2743
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