Chromatin-bound RB targets promoters, enhancers, and CTCF-bound loci and is redistributed by cell-cycle progression

Ioannis Sanidas, Hanjun Lee, Purva H. Rumde, Gaylor Boulay, Robert Morris, Gabriel Golczer, Marcelo Stanzione, Soroush Hajizadeh, Jun Zhong, Meagan B. Ryan, Ryan B. Corcoran, Benjamin J. Drapkin, Miguel N. Rivera, Nicholas J. Dyson, Michael S. Lawrence

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The interaction of RB with chromatin is key to understanding its molecular functions. Here, for first time, we identify the full spectrum of chromatin-bound RB. Rather than exclusively binding promoters, as is often described, RB targets three fundamentally different types of loci (promoters, enhancers, and insulators), which are largely distinguishable by the mutually exclusive presence of E2F1, c-Jun, and CTCF. While E2F/DP facilitates RB association with promoters, AP-1 recruits RB to enhancers. Although phosphorylation in CDK sites is often portrayed as releasing RB from chromatin, we show that the cell cycle redistributes RB so that it enriches at promoters in G1 and at non-promoter sites in cycling cells. RB-bound promoters include the classic E2F-targets and are similar between lineages, but RB-bound enhancers associate with different categories of genes and vary between cell types. Thus, RB has a well-preserved role controlling E2F in G1, and it targets cell-type-specific enhancers and CTCF sites when cells enter S-phase.

Original languageEnglish (US)
Pages (from-to)3333-3349.e9
JournalMolecular cell
Volume82
Issue number18
DOIs
StatePublished - Sep 15 2022

Keywords

  • AP-1
  • cell-cycle regulation
  • CTCF
  • E2F
  • PanChIP
  • RB phosphorylation
  • RB-bound enhancers
  • RB-bound promoters
  • regulation of RB activity
  • retinoblastoma protein

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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