Distinct roles of BET Family Members in ERa Enhancer Function and Gene Regulation in Breast Cancer Cells [ChIP-seq]

Estrogen (E2)-dependent gene regulation mediated by estrogen receptor alpha (ERa) plays a mitogenic role in ER-positive breast cancer cells. Although clinical applications of selective estrogen receptor modulators (SERMs), which directly interact with ERa to alter ERa activity, have been effective as a first line of treatment for breast cancer patients, a large subset of the patients will develop resistance after prolonged use of SERMs. Thus, there is a great need to develop alternative therapeutic strategies for SERM-resistant breast cancers. Here, we describe the potential use of the bromodomain family member protein (BRD) selective bromodomain inhibitor, JQ1, to alter E2-dependent gene expression program and inhibit E2-dependent growth of breast cancer cells. We show that each family member has partially redundant roles as ERa coregulators that are required for ERa-mediated gene transcription. Furthermore, we demonstrate the function of BRD3 as a molecular sensor of total BRD activity by the compensatory control of its protein levels. In addition, BRD3 colocalizes with a subset of ERa binding sites (ERBSs) that are enriched for active enhancer features and associated with highly E2-induced genes. Collectively, we illustrate a critical role of the BET family members in ERa dependent gene expression. Overall design: ChIP-seq datasets for BRD3 were generated using MCF-7 cells treated with 100 nM E2 for 3 hours to determine BRD3-enriched ERa enhancers. Please note that each processed data was generated from both replicates (i.e *rep1 and *rep2 samples) and linked to the corresponding *rep1 sample records.