BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure [NRVM Expression]

ABSTRACT: 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 f

ORGANISM(S): Rattus norvegicus

SUBMITTER: James Bradner 

PROVIDER: E-GEOD-48111 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress