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| Status |
Public on Aug 06, 2013 |
| Title |
BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure [NRVM Expression] |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
|
| Summary |
Heart failure (HF) is driven via interplay between master regulatory transcription factors and dynamic alterations in chromatin structure. While pathologic gene transactivation in this context is known to be associated with recruitment of histone acetyl-transferases and local chromatin hyperacetylation, the role of epigenetic reader proteins in cardiac biology is unknown. We therefore undertook a first study of acetyl-lysine reader proteins, or bromodomains, in HF. Using a chemical genetic approach, we establish a central role for BET-family bromodomain proteins in gene control during HF pathogenesis. BET inhibition potently suppresses cardiomyocyte hypertrophy in vitro and pathologic cardiac remodeling in vivo. Integrative transcriptional and epigenomic analyses reveal that BET proteins function mechanistically as pause-release factors critical to activation of canonical master regulators and effectors that are central to HF pathogenesis and relevant to the pathobiology of failing human hearts. This study implicates epigenetic readers in cardiac biology and identifies BET co-activator proteins as therapeutic targets in HF.
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| Overall design |
Gene expression analysis of neonatal rat ventricular mycotes (NRVM) subjected to phenylephrine (PE) treatment followed by treatment with vehicle (DMSO) or the BET bromodomain inhibitor JQ1
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| Contributor(s) |
Anand P, Brown JD, Lin CY, Qi J, Lemieux M, Bradner J, Haldar SM |
| Citation(s) |
23911322 |
| Submission date |
Jun 19, 2013 |
| Last update date |
Jul 31, 2017 |
| Contact name |
James Bradner |
| E-mail(s) |
bradner_computation@dfci.harvard.edu
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| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
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| Lab |
Bradner Lab
|
| Street address |
450 Brookline
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE48112 |
BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure |
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| Relations |
| BioProject |
PRJNA208939 |
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