Histone H2A Ubiquitination Reinforces Mechanical Stability and Asymmetry at the Single-Nucleosome Level
Histone H2A Ubiquitination Reinforces Mechanical Stability and Asymmetry at the Single-Nucleosome Level
复制标题
组蛋白 H2A 泛素化增强单核小体水平的机械稳定性和不对称性
DOI：
10.1021/jacs.9b12448
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发表时间：
2020
影响因子：
15
通讯作者：
Li Wei
中科院分区：
文献类型：
--
作者：
Xiao Xue;Liu Cuifang;Pei Yingxin;Wang Yi-Zhou;Kong Jingwei;Lu Ke;Ma Lu;Dou Shuo-Xing;Wang Peng-Ye;Li Guohong;Chen Ping;Li Wei
组蛋白H2A （ubH2A）赖氨酸119处的单泛素化是一种普遍的翻译后修饰，与染色质中的基因抑制有关。然而，人们对ubH2A在核小体上的直接作用知之甚少。在这里，我们使用单分子磁镊子确定了ubH2A对核小体的影响。我们发现ubH2A通过阻断组蛋白八聚体DNA的剥离来稳定核小体。每个ubH2A加强了一半的外包裹层，并为核小体展开引入了强大的不对称性。此外，实时去泛素化过程证实，ubh2a -核小体被依次去泛素化并恢复到未修饰的核小体状态。这些结果为理解基因转录或复制过程中RNA或DNA聚合酶通过ubh2a -核小体屏障的抑制提供了新的机制。
Monoubiquitination at lysine 119 of histone H2A (ubH2A) is a prevalent post-translational modification that is associated with gene repression in the context of chromatin. However, the direct function of ubH2A on nucleosome is poorly understood. Here we identified the effect of ubH2A on nucleosome using single-molecule magnetic tweezers. We revealed that ubH2A stabilizes the nucleosome by blocking the peeling of DNA from the histone octamer. Each ubH2A reinforces one-half of the outer wrap and introduces a robust asymmetry for nucleosome unfolding. Furthermore, a real-time deubiquitination process confirmed that ubH2A-nucleosome is sequentially deubiquitinated and restored to the unmodified nucleosome state. These results provide a novel mechanism to understand the repression of the passage of RNA or DNA polymerases through the ubH2A-nucleosome barrier during gene transcription or replication.