EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent

被引：49

作者：

Ai, Shanshan ^{[1
]}

Peng, Yong ^{[1
]}

Li, Chen ^{[1
]}

Gu, Fei ^{[2
]}

Yu, Xianhong ^{[1
]}

Yue, Yanzhu ^{[1
]}

Ma, Qing ^{[2
]}

Chen, Jinghai ^{[2
]}

Lin, Zhiqiang ^{[2
]}

Zhou, Pingzhu ^{[2
]}

Xie, Huafeng ^{[3
,7
]}

Prendiville, Terence W. ^{[2
]}

Zheng, Wen ^{[1
]}

Liu, Yuli ^{[1
]}

Orkin, Stuart H. ^{[3
,4
,5
,7
]}

Wang, Da-Zhi ^{[2
,4
]}

Yu, Jia ^{[6
]}

Pu, William T. ^{[2
,4
]}

He, Aibin ^{[1
]}

机构：

[1] Peking Univ, Beijing Key Lab Cardiometab Mol Med, PekingTsinghua Ctr Life Sci, Inst Mol Med, Beijing, Peoples R China

[2] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA

[3] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA

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

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

[6] Peking Union Med Coll, Chinese Acad Med Sci, Inst Basic Med Sci, Dept Biochem & Mol Biol,State Key Lab Med Mol Bio, Beijing, Peoples R China

[7] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

来源：

ELIFE | 2017年 / 6卷

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

II HISTONE DEACETYLASES; CARDIAC MYOCYTE PROLIFERATION; READ ALIGNMENT; PROTEIN EED; STEM-CELLS; CHROMATIN; CARDIOMYOCYTE; REPRESSION; ACETYLATION; HYPERTROPHY;

D O I：

10.7554/eLife.24570

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

In proliferating cells, where most Polycomb repressive complex 2 (PRC2) studies have been performed, gene repression is associated with PRC2 trimethylation of H3K27 (H3K27me3). However, it is uncertain whether PRC2 writing of H3K27me3 is mechanistically required for gene silencing. Here, we studied PRC2 function in postnatal mouse cardiomyocytes, where the paucity of cell division obviates bulk H3K27me3 rewriting after each cell cycle. EED (embryonic ectoderm development) inactivation in the postnatal heart (Eed(CKO)) caused lethal dilated cardiomyopathy. Surprisingly, gene upregulation in Eed(CKO) was not coupled with loss of H3K27me3. Rather, the activating histone mark H3K27ac increased. EED interacted with histone deacetylases (HDACs) and enhanced their catalytic activity. HDAC overexpression normalized Eed(CKO) heart function and expression of derepressed genes. Our results uncovered a non-canonical, H3K27me3-independent EED repressive mechanism that is essential for normal heart function. Our results further illustrate that organ dysfunction due to epigenetic dysregulation can be corrected by epigenetic rewiring.

引用

页数：22

共 61 条

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