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
{"title":"非分裂细胞中向催化活性较低的Polycomb抑制复合物的保守转换。","authors":"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","doi":"10.1016/j.celrep.2024.115192","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115192"},"PeriodicalIF":7.5000,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells.\",\"authors\":\"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\",\"doi\":\"10.1016/j.celrep.2024.115192\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":9798,\"journal\":{\"name\":\"Cell reports\",\"volume\":\"44 1\",\"pages\":\"115192\"},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2025-01-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell reports\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.celrep.2024.115192\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2024.115192","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
A conserved switch to less catalytically active Polycomb repressive complexes in non-dividing cells.
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.
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.
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