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

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Author
Ai, Shanshan
Peng, Yong
Li, Chen
Gu, Fei
Yu, Xianhong
Yue, Yanzhu
Ma, Qing
Chen, Jinghai
Lin, Zhiqiang
Zhou, Pingzhu
Xie, Huafeng
Prendiville, Terence W
Zheng, Wen
Liu, Yuli
Wang, Da-Zhi
Yu, Jia
He, Aibin
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.7554/eLife.24570Metadata
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Ai, S., Y. Peng, C. Li, F. Gu, X. Yu, Y. Yue, Q. Ma, et al. 2017. “EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent.” eLife 6 (1): e24570. doi:10.7554/eLife.24570. http://dx.doi.org/10.7554/eLife.24570.Abstract
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 (EedCKO) caused lethal dilated cardiomyopathy. Surprisingly, gene upregulation in EedCKO 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 EedCKO 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. DOI: http://dx.doi.org/10.7554/eLife.24570.001Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400508/pdf/Terms of Use
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