A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-01-11 DOI:10.1016/j.celrep.2024.115192

Rachel McCole, James Nolan, David M Reck, Craig Monger, Samantha Rustichelli, Eric Conway, Gerard L Brien, Cheng Wang, Orla Deevy, Hannah K Neikes, Frances M Bashore, Aoibhinn Mooney, Richard Flavin, Elisabeth Vandenberghe, Sarena F Flanigan, Diego Pasini, Chen Davidovich, Michiel Vermeulen, Lindsey I James, Evan Healy, Adrian P Bracken

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引用次数: 0

Abstract

Polycomb repressive complex 2 (PRC2), composed of the core subunits EED, SUZ12, and either EZH1 or EZH2, is critical for maintaining cellular identity in multicellular organisms. PRC2 deposits H3K27me3, which is thought to recruit the canonical form of PRC1 (cPRC1) to promote gene repression. Here, we show that EZH1-PRC2 and cPRC1 are the primary Polycomb complexes on target genes in non-dividing, quiescent cells. Furthermore, these cells are resistant to PRC2 inhibitors. While PROTAC-mediated degradation of EZH1-PRC2 in quiescent cells does not reduce H3K27me3, it partially displaces cPRC1. Our results reveal an evolutionarily conserved switch to less catalytically active Polycomb complexes in non-dividing cells and raise concerns about using PRC2 inhibitors in cancers with significant populations of non-dividing cells.

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.