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中国科学家揭示组蛋白变体H2A.Z对DNA复制起始位点的调控
2019-12-26 14:42

近日,中国科学院生物物理研究所的李国红课题组与朱明昭课题组合作揭示组蛋白变体H2A.Z对DNA复制起始位点的调控。2019年12月25日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员发现,在HeLa细胞中,含有组蛋白变体H2A.Z的核小体富含在其赖氨酸20残基(H4K20me2)上二甲基化的组蛋白H4和结合的起源识别复合物(ORC)。体外研究表明,含H2A.Z的核小体直接与组蛋白赖氨酸甲基转移酶SUV420H1结合,促进了H4K20me2的沉积,而这又是ORC1结合所必需的。

全基因组研究表明,来自H4K20me2、ORC1和新生DNA链的信号与H2A.Z共定位,并且H2A.Z的敲低导致整个基因组中H4K20me2、ORC1和新生链信号的减少。与其他来源相比,H2A.Z调控的复制起点具有更高的激发效率和更早的复制时机。这些结果表明,组蛋白变体H2A.Z在表观遗传学上调控早期复制起点的许可和激活,并通过SUV420H1-H4K20me2-ORC1信号轴维持复制时机。

研究人员表示,DNA复制是一个严格调控的过程,可确保在细胞周期中精确复制基因组。在真核生物中,复制起点的许可和激活受DNA序列和染色质特征的调节。但是,基于染色质的调节机制仍未完全表征。

附:英文原文

Title: H2A.Z facilitates licensing and activation of early replication origins

Author: Haizhen Long, Liwei Zhang, Mengjie Lv, Zengqi Wen, Wenhao Zhang, Xiulan Chen, Peitao Zhang, Tongqing Li, Luyuan Chang, Caiwei Jin, Guozhao Wu, Xi Wang, Fuquan Yang, Jianfeng Pei, Ping Chen, Raphael Margueron, Haiteng Deng, Mingzhao Zhu, Guohong Li

Issue&Volume: 2019-12-25

Abstract: DNA replication is a tightly regulated process that ensures the precise duplication of the genome during the cell cycle1. In eukaryotes, the licensing and activation of replication origins are regulated by both DNA sequence and chromatin features2. However, the chromatin-based regulatory mechanisms remain largely uncharacterized. Here we show that, in HeLa cells, nucleosomes containing the histone variant H2A.Z are enriched with histone H4 that is dimethylated on its lysine 20 residue (H4K20me2) and with bound origin-recognition complex (ORC). In vitro studies show that H2A.Z-containing nucleosomes bind directly to the histone lysine methyltransferase enzyme SUV420H1, promoting H4K20me2 deposition, which is in turn required for ORC1 binding. Genome-wide studies show that signals from H4K20me2, ORC1 and nascent DNA strands co-localize with H2A.Z, and that depletion of H2A.Z results in decreased H4K20me2, ORC1 and nascent-strand signals throughout the genome. H2A.Z-regulated replication origins have a higher firing efficiency and early replication timing compared with other origins. Our results suggest that the histone variant H2A.Z epigenetically regulates the licensing and activation of early replication origins and maintains replication timing through the SUV420H1–H4K20me2–ORC1 axis.

DOI: 10.1038/s41586-019-1877-9

Source: https://www.nature.com/articles/s41586-019-1877-9

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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