|
| Status |
Public on Oct 06, 2016 |
| Title |
Signal-Dependent Recruitment of BRD4 to Cardiomyocyte Super-Enhancers is Suppressed by a MicroRNA [RNA-Seq] |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
BRD4 governs pathological cardiac gene expression by binding acetylated chromatin, resulting in enhanced RNA polymerase II (Pol II) phosphorylation and transcription elongation. Here, we describe a signal-dependent mechanism for regulation of BRD4 in cardiomyocytes. BRD4 expression is suppressed by microRNA-9 (miR-9), which targets the 3’ untranslated region of the Brd4 transcript. In response to stress stimuli, miR-9 is downregulated, leading to derepression of BRD4 and enrichment of BRD4 at long-range super-enhancers (SEs) associated with pathological cardiac genes. A miR-9 mimic represses stimulus-dependent targeting of BRD4 to SEs and blunts Pol II phosphorylation at proximal transcription start sites, without affecting BRD4 binding to SEs that control constitutively expressed cardiac genes. These findings suggest that dynamic enrichment of BRD4 at SEs genome-wide serves a crucial role in the control of stress-induced cardiac gene expression, and define a miR-dependent signaling mechanism for the regulation of chromatin state and Pol II phosphorylation.
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| |
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| Overall design |
RNA-seq in neonatal rat ventricular myocytes
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| |
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| Contributor(s) |
McKinsey TA, Stratton MS, Halder SM, Lin CC, Bradner JE |
| Citation missing |
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| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 HL127240 |
Regulation of Chromatin Signaling in Heart Failure by BET Bromodomain Proteins |
UNIVERSITY OF COLORADO DENVER |
McKinsey |
| F32 HL126354 |
Role of BET proteins in cardiac remodeling |
UNIVERSITY OF COLORADO DENVER |
Stratton |
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| |
| Submission date |
Jun 10, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Timothy McKinsey |
| E-mail(s) |
TIMOTHY.MCKINSEY@UCDENVER.EDU
|
| Phone |
303-724-5479
|
| Organization name |
University of Colorado Anschutz Medical Campus
|
| Department |
Division of Cardiology
|
| Lab |
McKinsey
|
| Street address |
12700 E. 19th Ave (8450E)
|
| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE83230 |
Signal-Dependent Recruitment of BRD4 to Cardiomyocyte Super-Enhancers is Suppressed by a MicroRNA |
|
| Relations |
| BioProject |
PRJNA325308 |
| SRA |
SRP076389 |
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