|
| Status |
Public on Apr 14, 2017 |
| Title |
EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| |
|
| Overall design |
Refer to individual Series
|
| |
|
| Citation(s) |
28394251 |
| |
| Submission date |
Oct 06, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Yong Peng |
| E-mail(s) |
yongp@outlook.com
|
| Organization name |
University of Chicago
|
| Department |
Department of Chemistry
|
| Lab |
Chuan He
|
| Street address |
929 E 57th Street
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60615 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (75)
|
|
| This SuperSeries is composed of the following SubSeries:
|
| GSE73677 |
Transcriptional repression by non-canonical EED stimulation of histone deacetylase activity is required for heart maturation independently of H3K27me3 [Microarray] |
| GSE73769 |
Transcriptional repression by non-canonical EED stimulation of histone deacetylase activity is required for heart maturation independently of H3K27me3 [ChIP-seq] |
| GSE86868 |
Transcriptional repression by non-canonical EED stimulation of histone deacetylase activity is required for heart maturation independently of H3K27me3 [RNA-seq] |
| GSE89585 |
Transcriptional repression by non-canonical EED stimulation of histone deacetylase activity is required for heart maturation independently of H3K27me3 [RNA-seq for EED and HDAC rescue] |
|
| Relations |
| BioProject |
PRJNA297865 |
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