通过染色质上的二聚化激活自动甲基化的 PRC2

IF 14.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Cell Pub Date : 2024-09-19 DOI:10.1016/j.molcel.2024.08.025
Paul V. Sauer, Egor Pavlenko, Trinity Cookis, Linda C. Zirden, Juliane Renn, Ankush Singhal, Pascal Hunold, Michaela N. Hoehne-Wiechmann, Olivia van Ray, Farnusch Kaschani, Markus Kaiser, Robert Hänsel-Hertsch, Karissa Y. Sanbonmatsu, Eva Nogales, Simon Poepsel
{"title":"通过染色质上的二聚化激活自动甲基化的 PRC2","authors":"Paul V. Sauer, Egor Pavlenko, Trinity Cookis, Linda C. Zirden, Juliane Renn, Ankush Singhal, Pascal Hunold, Michaela N. Hoehne-Wiechmann, Olivia van Ray, Farnusch Kaschani, Markus Kaiser, Robert Hänsel-Hertsch, Karissa Y. Sanbonmatsu, Eva Nogales, Simon Poepsel","doi":"10.1016/j.molcel.2024.08.025","DOIUrl":null,"url":null,"abstract":"<p>Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit enhancer of zeste homolog 2 (EZH2) stimulates its activity by an unknown mechanism. Here, we show that human PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosteric <em>trans</em>-autoactivation via EED, suggesting a previously unknown mechanism mediating context-dependent activation of PRC2. Our work showcases the molecular mechanism of auto-modification-coupled dimerization in the regulation of chromatin-modifying complexes.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"64 1","pages":""},"PeriodicalIF":14.5000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Activation of automethylated PRC2 by dimerization on chromatin\",\"authors\":\"Paul V. Sauer, Egor Pavlenko, Trinity Cookis, Linda C. Zirden, Juliane Renn, Ankush Singhal, Pascal Hunold, Michaela N. Hoehne-Wiechmann, Olivia van Ray, Farnusch Kaschani, Markus Kaiser, Robert Hänsel-Hertsch, Karissa Y. Sanbonmatsu, Eva Nogales, Simon Poepsel\",\"doi\":\"10.1016/j.molcel.2024.08.025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit enhancer of zeste homolog 2 (EZH2) stimulates its activity by an unknown mechanism. Here, we show that human PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosteric <em>trans</em>-autoactivation via EED, suggesting a previously unknown mechanism mediating context-dependent activation of PRC2. Our work showcases the molecular mechanism of auto-modification-coupled dimerization in the regulation of chromatin-modifying complexes.</p>\",\"PeriodicalId\":18950,\"journal\":{\"name\":\"Molecular Cell\",\"volume\":\"64 1\",\"pages\":\"\"},\"PeriodicalIF\":14.5000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.molcel.2024.08.025\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.molcel.2024.08.025","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

多聚胞抑制复合体 2(PRC2)是一种表观遗传调控因子,可对组蛋白 3 的 27 号赖氨酸(H3K27me3)进行三甲基化,对胚胎发育和细胞分化至关重要。H3K27me3 与转录抑制染色质有关,当 PRC2 被调节亚基 EED 结合甲基赖氨酸后异源激活时,H3K27me3 就会形成。催化亚基泽斯特同源增强子 2(EZH2)的自甲基化通过一种未知的机制刺激其活性。在这里,我们展示了人类 PRC2 在染色质上形成的二聚体,其中一个非活性、自甲基化的 PRC2 原体是第二个 PRC2 的异位激活剂,后者准备甲基化底物核小体的 H3。功能测试支持了我们通过 EED 进行异生反式自激活的模型,这表明了一种以前未知的介导 PRC2 上下文依赖性激活的机制。我们的工作展示了自动修饰耦合二聚化在调控染色质修饰复合物中的分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Activation of automethylated PRC2 by dimerization on chromatin

Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit enhancer of zeste homolog 2 (EZH2) stimulates its activity by an unknown mechanism. Here, we show that human PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosteric trans-autoactivation via EED, suggesting a previously unknown mechanism mediating context-dependent activation of PRC2. Our work showcases the molecular mechanism of auto-modification-coupled dimerization in the regulation of chromatin-modifying complexes.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Molecular Cell
Molecular Cell 生物-生化与分子生物学
CiteScore
26.00
自引率
3.80%
发文量
389
审稿时长
1 months
期刊介绍: Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.
期刊最新文献
AMPK: Balancing mitochondrial quality and quantity through opposite regulation of mitophagy pathways A major step forward toward high-resolution nanopore sequencing of full-length proteins m6A sites in the coding region trigger translation-dependent mRNA decay Flipping a switch on BRD4: How to control the do-it-all Lost in translation: Threonine dictates aggregation of CAT tails
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1