Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1

Li Huang; Youwang Wang; Haizhen Long; Haoqiang Zhu; Zengqi Wen; Liwei Zhang; Wenhao Zhang; Zhenqian Guo; Longge Wang; Fangyi Tang; Jie Hu; Keyan Bao; Ping Zhu; Guohong Li; Zheng Zhou

doi:10.1016/j.molcel.2023.07.001

Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1

Mol Cell. 2023 Aug 17;83(16):2884-2895.e7. doi: 10.1016/j.molcel.2023.07.001. Epub 2023 Aug 2.

Authors

Li Huang¹, Youwang Wang¹, Haizhen Long², Haoqiang Zhu¹, Zengqi Wen³, Liwei Zhang⁴, Wenhao Zhang⁵, Zhenqian Guo⁴, Longge Wang¹, Fangyi Tang¹, Jie Hu¹, Keyan Bao¹, Ping Zhu⁶, Guohong Li⁷, Zheng Zhou⁸

Affiliations

¹ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen 518132, China. Electronic address: longhaizhen@szbl.ac.cn.
³ School of Medicine, Sun Yat-sen University, Shenzhen 518107, China.
⁴ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
⁵ Ministry of Education (MOE) Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
⁶ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: zhup@ibp.ac.cn.
⁷ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430072, China. Electronic address: liguohong@sun5.ibp.ac.cn.
⁸ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: zhouzh@ibp.ac.cn.

PMID: 37536340
DOI: 10.1016/j.molcel.2023.07.001

Abstract

DNA replication ensures the accurate transmission of genetic information during the cell cycle. Histone variant H2A.Z is crucial for early replication origins licensing and activation in which SUV420H1 preferentially recognizes H2A.Z-nucleosome and deposits H4 lysine 20 dimethylation (H4K20me2) on replication origins. Here, we report the cryo-EM structures of SUV420H1 bound to H2A.Z-nucleosome or H2A-nucleosome and demonstrate that SUV420H1 directly interacts with H4 N-terminal tail, the DNA, and the acidic patch in the nucleosome. The H4 (1-24) forms a lasso-shaped structure that stabilizes the SUV420H1-nucleosome complex and precisely projects the H4K20 residue into the SUV420H1 catalytic center. In vitro and in vivo analyses reveal a crucial role of the SUV420H1 KR loop (residues 214-223), which lies close to the H2A.Z-specific residues D97/S98, in H2A.Z-nucleosome preferential recognition. Together, our findings elucidate how SUV420H1 recognizes nucleosomes to ensure site-specific H4K20me2 modification and provide insights into how SUV420H1 preferentially recognizes H2A.Z nucleosome.

Keywords: DNA replication initiation; H2A.Z-nucleosome; H4K20me2; SUV420H1; cryo-EM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA / metabolism
DNA Replication
Histones* / metabolism
Methylation
Nucleosomes* / genetics

Substances

Histones
Nucleosomes
DNA