Resistance of estrogen receptor function to BET bromodomain inhibition is mediated by transcriptional coactivator cooperativity. Resistance of estrogen receptor function to BET bromodomain inhibition is mediated by transcriptional coactivator cooperativity

BRD4, a member of the BET family, can bind to ER binding sites and activate transcription of BETi-resistant genes, such as MYC, independently of bromodomains. Importantly, we uncover that the bromodomain-independent recruitment of BRD4 to enhancers relies on the Mediator complex, and that disruption of Mediator complex reduces BRD4's enhancer occupancy. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for BRD4 in MCF7 cells. DNase-seq in BRD4-dTAG cells. DNase-seq in BRD4-dTAG cells.