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

TY - JOUR

T1 - Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome

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.

UR - http://dx.doi.org/10.1016/j.str.2019.10.016

U2 - 10.1016/j.str.2019.10.016

DO - 10.1016/j.str.2019.10.016

M3 - Article

SN - 0969-2126

VL - 28

SP - 44

EP - 53

JO - Structure

JF - Structure

IS - 1

M1 - e4

ER -