Super-enhancers define a proliferative PGC-1α-expressing melanoma subgroup sensitive to BET inhibition.

ABSTRACT: Metabolic changes are linked to epigenetic reprogramming and play important roles in several tumor types. PGC-1α is a transcriptional coactivator controlling mitochondrial biogenesis and is linked to oxidative phosphorylation. We provide evidence that melanoma models with elevated PGC-1α levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra-terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1α gene. BET inhibitor treatment prevented this interaction, leading to a dramatic reduction of PGC-1α expression. Accordingly, BET inhibition diminished respiration and mitochondrial function in cells. In vivo, melanoma models with high PGC-1α expression strongly respon

SUBMITTER: Gelato KA 

PROVIDER: S-EPMC5799712 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature