Genomics

Dataset Information

24

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


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 PCR2 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. Overall design: Refer to individual Series

INSTRUMENT(S): [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]

SUBMITTER: Yong Peng  

PROVIDER: GSE73771 | GEO | 2017-04-14

SECONDARY ACCESSION(S): GSE73677 GSE89585PRJNA297865 GSE73769 GSE86868

REPOSITORIES: GEO

altmetric image

Publications


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 pos  ...[more]

Similar Datasets

| GSE73769 | GEO
| GSE89585 | GEO
| GSE86868 | GEO
| GSE73677 | GEO
2014-01-23 | E-GEOD-42566 | ArrayExpress
| GSE42566 | GEO
| GSE102702 | GEO
| GSE81267 | GEO
| phs000792 | dbGaP
2014-08-28 | E-GEOD-49305 | ArrayExpress