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. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for BRD4 in MCF7 cells. DNase-seq in BRD4-dTAG cells. DNase-seq in BRD4-dTAG cells.