Structural basis for linker histone H5-nucleosome binding and chromatin fiber compaction  

作　　者：Wenyan Li Jie Hu Feng Song Juan Yu Xin Peng Shuming Zhang Lin Wang Mingli Hu Jia-Cheng Liu Yu Wei Xue Xiao Yan Li Dongyu Li Hui Wang Bing-Rui Zhou Linchang Dai Zongjun Mou Min Zhou Haonan Zhang Zheng Zhou Huidong Zhang Yawen Bai Jin-Qiu Zhou Wei Li Guohong Li Ping Zhu 

机构地区：[1]Key Laboratory of Epigenetic Regulation and Intervention,Institute of Biophysics,Chinese Academy of Sciences,Bejing,China [2]University of Chinese Academy of Sciences,Beijing,China [3]New Cornerstone Science Laboratory,Frontier Science Center for Immunology and Metabolism,Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,Taikang Center for Life and Medical Sciences,Wuhan University,Wuhan,Hubei,China [4]Shandong Key Laboratory of Biophysics,Institute of Biophysics,Dezhou University,Dezhou,Shangdong,China [5]Department of Public Health Laboratory Sciences,West China School of Public Health,Sichuan University,Chengdu,Sichuan,China [6]The State Key Laboratory of Molecular Biology,CAS Center for Excellence in Molecular CellScience,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,Shanghai,China [7]National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics,Institute of Physics,Chinese Academy of Sciences,Bejing,China [8]Laboratory of Biochemistry and Molecular Biology,National Cancer Institute,National Institutes of Health,Bethesda,MD,USA [9]Research Center for Environment and Female Reproductive Health,The Eighth Affliated Hospital,Sun Yat-sen University,Shenzhen,Guangdong,China.

出　　处：《Cell Research》2024年第10期707-724,共18页细胞研究（英文版）

基　　金：supported by grants from the Ministry of Science and Technology of China(2023YFA0913400 to P.Z.and G.L.,and 2021YFA1300100 to P.Z.);the National Natural Science Foundation of China(31991161 and 32230020 to G.L.,32241029 and 31730023 to P.Z.,and 31500606 and 62131004 to F.S.);the Chinese Academy of Sciences Strategic Priority Research Program(XDB37010100 to P.Z.);supported by the Beijing Municipal Science and Technology Committee(Z221100007022001);the Fundamental Research Funds for the Central Universities(2042022dx0003);HHMI international research scholar grant(55008737)to G.L.;Taishan Young Scholars Program of Shandong Province(TSQN20161049)to F.S.Y.B.;B.Z.are supported by the intramural research program of the National Cancer Institute,National Institutes of Health,USA.

摘　　要：The hierarchical packaging of chromatin fibers plays a critical role in gene regulation.The 30-nm chromatin fibers,a central-level structure bridging nucleosomal arrays to higher-order organizations,function as the first level of transcriptional dormant chromatin.The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA.Here,we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome,i.e.,the chromatin fiber reconstituted in the presence of linker histone H5,which shows a two-start left-handed double helical structure twisted by tetranucleosomal units.An atomic structural model of the H5-bound chromatin fiber,including an intact chromatosome,is built,which provides structural details of the full-length linker histone H5,including its N-terminal domain and an HMG-motif-like C-terminal domain.The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber.More importantly,the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions.In addition,we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments.Furthermore,our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber.These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatinfiberwithapolarity invitroand invivo.

关 键 词：chromato fibers polarity 

分 类 号：O17[理学—数学]