H2AK119ub1 differentially fine-tunes gene expression by modulating canonical PRC1-and H1-dependent chromatin compaction

作者全名：Zhao, Jicheng; Lan, Jie; Wang, Min; Liu, Cuifang; Fang, Zheng; Song, Aoqun; Zhang, Tiantian; Wang, Liang; Zhu, Bing; Chen, Ping; Yu, Juan; Li, Guohong

作者地址：[Zhao, Jicheng; Wang, Min; Liu, Cuifang; Song, Aoqun; Zhang, Tiantian; Zhu, Bing; Chen, Ping; Yu, Juan; Li, Guohong] Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromolecules, Natl Lab Biomacromolecules, Beijing 100101, Peoples R China; [Lan, Jie] Chongqing Med Univ, Sch Basic Med Sci, Dept Bioinformat, Chongqing 400016, Peoples R China; [Fang, Zheng; Li, Guohong] Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China; [Wang, Liang] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Beijing Frontier Res Ctr Biol Struct, Sch Life Sci, Beijing 100101, Peoples R China; [Zhu, Bing; Li, Guohong] Univ Chinese Acad Sci, Beijing 100049, Peoples R China; [Chen, Ping] Capital Med Univ, Sch Basic Med Sci, Dept Immunol, Beijing 100069, Peoples R China; [Li, Guohong] Wuhan Univ, Coll Life Sci, Frontier Sci Ctr Immunol & Metab, Taikang Ctr Life & Med Sci,New Cornerstone Sci Lab, Wuhan 430072, Peoples R China

通信作者：Chen, P; Yu, J; Li, GH (通讯作者)，Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromolecules, Natl Lab Biomacromolecules, Beijing 100101, Peoples R China.; Li, GH (通讯作者)，Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China.; Li, GH (通讯作者)，Univ Chinese Acad Sci, Beijing 100049, Peoples R China.; Chen, P (通讯作者)，Capital Med Univ, Sch Basic Med Sci, Dept Immunol, Beijing 100069, Peoples R China.; Li, GH (通讯作者)，Wuhan Univ, Coll Life Sci, Frontier Sci Ctr Immunol & Metab, Taikang Ctr Life & Med Sci,New Cornerstone Sci Lab, Wuhan 430072, Peoples R China.

来源：MOLECULAR CELL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001224210100001

JCR分区：Q1

影响因子：14.5

年份：2024

卷号：84

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Polycomb repressive complex 1 (PRC1) is a key transcriptional regulator in development via modulating chromatin structure and catalyzing histone H2A ubiquitination at Lys119 (H2AK119ub1). H2AK119ub1 is one of the most abundant histone modifications in mammalian cells. However, the function of H2AK119ub1 in polycomb-mediated gene silencing remains debated. In this study, we reveal that H2AK119ub1 has two distinct roles in gene expression, through differentially modulating chromatin compaction mediated by canonical PRC1 and the linker histone H1. Interestingly, we find that H2AK119ub1 plays a positive role in transcription through interfering with the binding of canonical PRC1 to nucleosomes and therefore counteracting chromatin condensation. Conversely, we demonstrate that H2AK119ub1 facilitates H1 -dependent chromatin condensation and enhances the silencing of developmental genes in mouse embryonic stem cells, suggesting that H1 may be one of several possible pathways for H2AK119ub1 in repressing transcription. These results provide insights and molecular mechanisms by which H2AK119ub1 differentially fine-tunes developmental gene expression.

基金机构：Chinese Academy of Sciences

基金资助正文：We are grateful to Ting Yao (National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences) for preparing materials and ordering reagents. This work was supported by grants from the National Natural Science Foundation of China (31991161 and 32230020 to G.L.) , the Ministry of Science and Technology of China (2023YFA0913402 to G.L. and 2019YFA0508903 to J.Z.) , the National Natural Science Foundation of China (32270614 and 32070604 to J.Z., 32022014 to P.C., 32100470 to C.L.) , the Beijing Municipal Science and Technology to G.L. (Z221100007022001) , the Fundamental Research Funds for the Central Universities to G.L. (2042022dx0003) , and the Basic Research Program of the Chinese Academy of Sciences Based on Major Scientific Infrastructures to G.L. (JZHKYPT-2021- 05) . This paper has been supported by the New Cornerstone Science Foundation. All EM and fluorescent images were collected and processed at the Center for Bio-imaging, Core Facility for Protein Sciences, Institute of Biophysics,and Chinese Academy of Sciences. We are also indebted to the colleagues whose work could not be cited due to the limitation of space.r and Chinese Academy of Sciences. We are also indebted to the colleagues whose work could not be cited due to the limitation of space.