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

Yoshimasa Takizawa; Cheng-Han Ho; Hiroaki Tachiwana; Hideyuki Matsunami; Wataru Kobayashi; Midori Suzuki; Yasuhiro Arimura; Tetsuya Hori; Tatsuo Fukagawa; Melanie D. Ohi; Matthias Wolf; Hitoshi Kurumizaka

doi:10.1016/j.str.2019.10.016

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

Yoshimasa Takizawa, Cheng-Han Ho, Hiroaki Tachiwana, Hideyuki Matsunami, Wataru Kobayashi, Midori Suzuki, Yasuhiro Arimura, Tetsuya Hori, Tatsuo Fukagawa, Melanie D. Ohi, Matthias Wolf (Lead / Corresponding author), Hitoshi Kurumizaka (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e4
Pages (from-to)	44-53
Number of pages	15
Journal	Structure
Volume	28
Issue number	1
DOIs	https://doi.org/10.1016/j.str.2019.10.016
Publication status	Published - 7 Jan 2020

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title = "Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome",

abstract = "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.",

author = "Yoshimasa Takizawa and Cheng-Han Ho and Hiroaki Tachiwana and Hideyuki Matsunami and Wataru Kobayashi and Midori Suzuki and Yasuhiro Arimura and Tetsuya Hori and Tatsuo Fukagawa and Ohi, \{Melanie D.\} and Matthias Wolf and Hitoshi Kurumizaka",

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AU - Takizawa, Yoshimasa

AU - Ho, Cheng-Han

AU - Tachiwana, Hiroaki

AU - Matsunami, Hideyuki

AU - Kobayashi, Wataru

AU - Suzuki, Midori

AU - Arimura, Yasuhiro

AU - Hori, Tetsuya

AU - Fukagawa, Tatsuo

AU - Ohi, Melanie D.

AU - Wolf, Matthias

AU - Kurumizaka, Hitoshi

PY - 2020/1/7

Y1 - 2020/1/7

N2 - 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.

AB - 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.

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

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