Estrogen induces dynamic ERα and RING1B recruitment to control gene and enhancer activities in luminal breast cancer

Yusheng Zhang, Yusheng Zhang, Ho Lam Chan, Ho Lam Chan, Liliana Garcia-Martinez, Liliana Garcia-Martinez, Daniel L. Karl, Natalia Weich, Natalia Weich, Joyce M. Slingerland, Joyce M. Slingerland, Joyce M. Slingerland, Joyce M. Slingerland, Ramiro E. Verdun, Ramiro E. Verdun, Lluis Morey, Lluis Morey

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numberEAAZ7249
JournalScience Advances
Volume6
Issue number23
DOIs
StatePublished - Jun 2020

ASJC Scopus subject areas

  • General

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