期刊
SCIENCE ADVANCES
卷 6, 期 23, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaz7249
关键词
-
资金
- Sylvester Comprehensive Cancer Center funds
- AACR-Bayer Innovation and Discovery grant [18-80-44-MORE]
- Flight Attendant Medical Research Institute (FAMRI) Breast Cancer Developmental Grant
- American Cancer Society [IRG-17-183-16]
- Stanley J. Glaser Foundation Research Award [UM-SJG-2020-3]
- Leukemia and Lymphoma Society Specialized Center of Research grant (LLS-SCOR)
- Lampert Breast Cancer Research Fund
- National Cancer Institute of the National Institutes of Health [P30CA240139]
RING1B, a core Polycomb repressive complex 1 subunit, is a histone H2A ubiquitin ligase essential for development. RING1B is overexpressed in patients with luminal breast cancer (BC) and recruited to actively transcribed genes and enhancers co-occupied by the estrogen receptor alpha (ER alpha). Whether ER alpha-induced transcriptional programs are mediated by RING1B is not understood. We show that prolonged estrogen administration induces transcriptional output and chromatin landscape fluctuations. RING1B loss impairs full estrogen-mediated gene expression and chromatin accessibility for key BC transcription factors. These effects were mediated, in part, by RING1B enzymatic activity and nucleosome binding functions. RING1B is recruited in a cyclic manner to ER alpha, FOXA1, and GRHL2 cobound sites and regulates estrogen-induced enhancers and ER alpha recruitment. Last, ChIP exo revealed multiple binding events of these factors at single-nucleotide resolution, including RING1B occupancy approximately 10 base pairs around ER alpha bound sites. We propose RING1B as a key regulator of the dynamic, liganded-ER alpha transcriptional regulatory circuit in luminal BC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据