TY - JOUR
T1 - Estrogen induces dynamic ERα and RING1B recruitment to control gene and enhancer activities in luminal breast cancer
AU - Zhang, Yusheng
AU - Zhang, Yusheng
AU - Chan, Ho Lam
AU - Chan, Ho Lam
AU - Garcia-Martinez, Liliana
AU - Garcia-Martinez, Liliana
AU - Karl, Daniel L.
AU - Weich, Natalia
AU - Weich, Natalia
AU - Slingerland, Joyce M.
AU - Slingerland, Joyce M.
AU - Slingerland, Joyce M.
AU - Slingerland, Joyce M.
AU - Verdun, Ramiro E.
AU - Verdun, Ramiro E.
AU - Morey, Lluis
AU - Morey, Lluis
N1 - Publisher Copyright:
© 2020 The Authors.
PY - 2020/6
Y1 - 2020/6
N2 - 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 α (ERα). Whether ERα-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 ERα, FOXA1, and GRHL2 cobound sites and regulates estrogen-induced enhancers and ERα recruitment. Last, ChIP exo revealed multiple binding events of these factors at single-nucleotide resolution, including RING1B occupancy approximately 10 base pairs around ERα bound sites. We propose RING1B as a key regulator of the dynamic, liganded-ERα transcriptional regulatory circuit in luminal BC.
AB - 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 α (ERα). Whether ERα-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 ERα, FOXA1, and GRHL2 cobound sites and regulates estrogen-induced enhancers and ERα recruitment. Last, ChIP exo revealed multiple binding events of these factors at single-nucleotide resolution, including RING1B occupancy approximately 10 base pairs around ERα bound sites. We propose RING1B as a key regulator of the dynamic, liganded-ERα transcriptional regulatory circuit in luminal BC.
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U2 - 10.1126/sciadv.aaz7249
DO - 10.1126/sciadv.aaz7249
M3 - Article
C2 - 32548262
AN - SCOPUS:85086626627
VL - 6
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 23
M1 - EAAZ7249
ER -