Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1.
Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1.
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DOI：
10.1016/j.molcel.2023.07.001
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发表时间：
2023-07
期刊：
影响因子：
16
通讯作者：
Li Huang;Youwang Wang;Haizhen Long;Haoqiang Zhu;Zengqi Wen;Liwei Zhang;Wenhao Zhang;Zhenqian Guo;Longge Wang;Fang Tang;Jie Hu;Keyan Bao;P. Zhu;Guohong Li;Zheng Zhou
中科院分区：
文献类型：
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作者：
Li Huang;Youwang Wang;Haizhen Long;Haoqiang Zhu;Zengqi Wen;Liwei Zhang;Wenhao Zhang;Zhenqian Guo;Longge Wang;Fang Tang;Jie Hu;Keyan Bao;P. Zhu;Guohong Li;Zheng Zhou
DNA复制保证了细胞周期中遗传信息的准确传递。组蛋白变体 H2A.Z 对于早期复制起点许可和激活至关重要，其中 SUV420H1 优先识别 H2A.Z-核小体，并将 H4 赖氨酸 20 二甲基化 (H4K20me2) 沉积在复制起点上。在这里，我们报告了 SUV420H1 与 H2A.Z-核小体或 H2A-核小体结合的冷冻电镜结构，并证明 SUV420H1 直接与 H4 N 末端尾部、DNA 和核小体中的酸性补丁相互作用。 H4 (1–24) 形成套索形结构，可稳定 SUV420H1-核小体复合物，并将 H4K20 残基精确地投射到 SUV420H1 催化中心。体外和体内分析揭示了 SUV420H1 KR 环（残基 214–223）的关键作用，该环靠近 H2A.Z 特异性残基D97/S98，在H2A.Z-核小体中优先识别。总之，我们的研究结果阐明了 SUV420H1 如何识别核小体以确保位点特异性 H4K20me2 修饰，并提供有关 SUV420H1 如何优先识别 H2A.Z 核小体的见解。
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 vitroandin vivoanalyses 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.