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Distinct Roles of BET Family Members in ERα Enhancer Function and Gene Regulation in Breast Cancer Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109572 | GEO | 2019/09/25

REPOSITORIES: GEO

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

Project description:Estrogen (E2)-dependent gene regulation mediated by estrogen receptor alpha (ERα) plays a mitogenic role in ER-positive breast cancer cells. Although clinical applications of selective estrogen receptor modulators (SERMs), which directly interact with ERα to alter ERα 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 ERα coregulators that are required for ERα-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 ERα 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 ERα dependent gene expression.

2019-09-25 | GSE109571 | GEO

Distinct Roles of BET Family Members in ERα Enhancer Function and Gene Regulation in Breast Cancer Cells [RNA-seq]

2019-09-25 | GSE109570 | GEO