Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome.,Structure

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Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome.
Structure ( IF 5.7 ) Pub Date : 2019-11-08 , DOI: 10.1016/j.str.2019.10.016
Yoshimasa Takizawa ₁ , Cheng-Han Ho ₂ , Hiroaki Tachiwana ₃ , Hideyuki Matsunami ₄ , Wataru Kobayashi ₅ , Midori Suzuki ₆ , Yasuhiro Arimura ₇ , Tetsuya Hori ₈ , Tatsuo Fukagawa ₈ , Melanie D Ohi ₉ , Matthias Wolf ₄ , Hitoshi Kurumizaka ₁₀

Affiliation

Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Molecular Cryo-Electron Microscopy Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan.
Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Graduate School of Advanced Science & Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan; Department of Cancer Biology, The Cancer Institute of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
Molecular Cryo-Electron Microscopy Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan.
Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Graduate School of Advanced Science & Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Graduate School of Advanced Science & Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Life Science Institute, Cell & Developmental Biology, University of Michigan Medical School, 210 Washtenaw, Ann Arbor, MI 48109-2200, USA.
Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Graduate School of Advanced Science & Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.

The histone H3 variant CENP-A is a crucial epigenetic marker for centromere specification. CENP-A forms a characteristic nucleosome and dictates the higher-order configuration of centromeric chromatin. However, little is known about how the CENP-A nucleosome affects the architecture of centromeric chromatin. In this study, we reconstituted tri-nucleosomes mimicking a centromeric nucleosome arrangement containing the CENP-A nucleosome, and determined their 3D structures by cryoelectron microscopy. The H3-CENP-A-H3 tri-nucleosomes adopt an untwisted architecture, with an outward-facing linker DNA path between nucleosomes. This is distinct from the H3-H3-H3 tri-nucleosome architecture, with an inward-facing DNA path. Intriguingly, the untwisted architecture may allow the CENP-A nucleosome to be exposed to the solvent in the condensed chromatin model. These results provide a structural basis for understanding the 3D configuration of CENP-A-containing chromatin, and may explain how centromeric proteins can specifically target the CENP-A nucleosomes buried in robust amounts of H3 nucleosomes in centromeres.

中文翻译：

含有中央CENP-A核小体的着丝粒三核小体的Cryo-EM结构。

组蛋白H3变体CENP-A是着丝粒规格的重要表观遗传标记。CENP-A形成特征性核小体并决定着丝粒染色质的高阶构型。然而，关于CENP-A核小体如何影响着丝粒染色质的体系知之甚少。在这项研究中，我们重构了三核小体，模仿了包含CENP-A核小体的着丝粒核小体排列，并通过冷冻电子显微镜确定了其3D结构。H3-CENP-A-H3三核小体采用非扭曲结构，核小体之间具有向外的接头DNA路径。这与H3-H3-H3三核小体结构不同，具有向内的DNA路径。有趣的是，未扭曲的结构可以使CENP-A核小体在浓缩的染色质模型中暴露于溶剂中。

更新日期：2019-11-08

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