1. Chromatin-bound RB targets promoters, enhancers, and CTCF-bound loci and is redistributed by cell-cycle progression.
- Author
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Sanidas I, Lee H, Rumde PH, Boulay G, Morris R, Golczer G, Stanzione M, Hajizadeh S, Zhong J, Ryan MB, Corcoran RB, Drapkin BJ, Rivera MN, Dyson NJ, and Lawrence MS
- Subjects
- Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, E2F Transcription Factors genetics, E2F Transcription Factors metabolism, E2F1 Transcription Factor genetics, E2F1 Transcription Factor metabolism, Promoter Regions, Genetic, Transcription Factor AP-1 genetics, Chromatin genetics, Retinoblastoma Protein genetics, Retinoblastoma Protein metabolism
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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