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dc.contributor.authorAi, Shanshanen_US
dc.contributor.authorPeng, Yongen_US
dc.contributor.authorLi, Chenen_US
dc.contributor.authorGu, Feien_US
dc.contributor.authorYu, Xianhongen_US
dc.contributor.authorYue, Yanzhuen_US
dc.contributor.authorMa, Qingen_US
dc.contributor.authorChen, Jinghaien_US
dc.contributor.authorLin, Zhiqiangen_US
dc.contributor.authorZhou, Pingzhuen_US
dc.contributor.authorXie, Huafengen_US
dc.contributor.authorPrendiville, Terence Wen_US
dc.contributor.authorZheng, Wenen_US
dc.contributor.authorLiu, Yulien_US
dc.contributor.authorOrkin, Stuart Hen_US
dc.contributor.authorWang, Da-Zhien_US
dc.contributor.authorYu, Jiaen_US
dc.contributor.authorPu, William Ten_US
dc.contributor.authorHe, Aibinen_US
dc.date.accessioned2017-05-01T19:27:18Z
dc.date.issued2017en_US
dc.identifier.citationAi, 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.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32630546
dc.description.abstractIn 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.24570.001en
dc.language.isoen_USen
dc.publishereLife Sciences Publications, Ltden
dc.relation.isversionofdoi:10.7554/eLife.24570en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400508/pdf/en
dash.licenseLAAen_US
dc.subjectcardiologyen
dc.subjectgene regulationen
dc.subjectchromatinen
dc.subjectheart developmenten
dc.subjectMouseen
dc.titleEED orchestration of heart maturation through interaction with HDACs is H3K27me3-independenten
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journaleLifeen
dash.depositing.authorOrkin, Stuart Hen_US
dc.date.available2017-05-01T19:27:18Z
dc.identifier.doi10.7554/eLife.24570*
dash.authorsorderedfalse
dash.contributor.affiliatedPu, William
dash.contributor.affiliatedOrkin, Stuart


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