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High-Speed Atomic Force Microscopy Reveals Spontaneous Nucleosome Sliding of H2A.Z at the Subsecond Time Scale
Nano Letters ( IF 9.6 ) Pub Date : 2023-02-13 , DOI: 10.1021/acs.nanolett.2c04346
Shin Morioka 1 , Shoko Sato 2 , Naoki Horikoshi 2 , Tomoya Kujirai 2 , Takuya Tomita 1 , Yudai Baba 1 , Takahiro Kakuta 1, 3 , Tomoki Ogoshi 3, 4 , Leonardo Puppulin 3 , Ayumi Sumino 3, 5 , Kenichi Umeda 3 , Noriyuki Kodera 3 , Hitoshi Kurumizaka 2, 6 , Mikihiro Shibata 3, 5
Affiliation  

Nucleosome dynamics, such as nucleosome sliding and DNA unwrapping, are important for gene regulation in eukaryotic chromatin. H2A.Z, a variant of histone H2A that is highly evolutionarily conserved, participates in gene regulation by forming unstable multipositioned nucleosomes in vivo and in vitro. However, the subsecond dynamics of this unstable nucleosome have not been directly visualized under physiological conditions. Here, we used high-speed atomic force microscopy (HS-AFM) to directly visualize the subsecond dynamics of human H2A.Z.1-nucleosomes. HS-AFM videos show nucleosome sliding along 4 nm of DNA within 0.3 s in any direction. This sliding was also visualized in an H2A.Z.1 mutant, in which the C-terminal half was replaced by the corresponding canonical H2A amino acids, indicating that the interaction between the N-terminal region of H2A.Z.1 and the DNA is responsible for nucleosome sliding. These results may reveal the relationship between nucleosome dynamics and gene regulation by histone H2A.Z.

中文翻译:

高速原子力显微镜揭示了 H2A.Z 在亚秒级时间尺度上的自发核小体滑动

核小体动力学,例如核小体滑动和 DNA 展开,对于真核染色质中的基因调控非常重要。H2A.Z 是组蛋白 H2A 的一种变体,在进化上高度保守,通过在体内体外形成不稳定的多位核小体参与基因调控. 然而,这种不稳定核小体的亚秒动力学尚未在生理条件下直接可视化。在这里,我们使用高速原子力显微镜 (HS-AFM) 直接可视化人类 H2A.Z.1-核小体的亚秒动力学。HS-AFM 视频显示核小体在 0.3 秒内沿 4 nm 的 DNA 向任何方向滑动。这种滑动也在 H2A.Z.1 突变体中可见,其中 C 末端的一半被相应的规范 H2A 氨基酸取代,表明 H2A.Z.1 的 N 末端区域与 DNA 之间的相互作用负责核小体滑动。这些结果可能揭示了核小体动力学与组蛋白 H2A.Z 基因调控之间的关系。
更新日期:2023-02-13
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