The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism

Yasuhiro Arimura, Hiroaki Tachiwana, Hiroki Takagi, Tetsuya Hori, Hiroshi Kimura, Tatsuo Fukagawa and Hitoshi Kurumizaka ()
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Yasuhiro Arimura: The University of Tokyo
Hiroaki Tachiwana: Waseda University
Hiroki Takagi: The University of Tokyo
Tetsuya Hori: Osaka University
Hiroshi Kimura: Tokyo Institute of Technology
Tatsuo Fukagawa: Osaka University
Hitoshi Kurumizaka: The University of Tokyo

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Centromeric nucleosomes are composed of the centromere-specific histone H3 variant CENP-A and the core histones H2A, H2B, and H4. To establish a functional kinetochore, histone H4 lysine-20 (H4K20) must be monomethylated, but the underlying mechanism has remained enigmatic. To provide structural insights into H4K20 methylation, we here solve the crystal structure of a nucleosome containing an H3.1-CENP-A chimera, H3.1CATD, which has a CENP-A centromere targeting domain and preserves essential CENP-A functions in vivo. Compared to the canonical H3.1 nucleosome, the H3.1CATD nucleosome exhibits conformational changes in the H4 N-terminal tail leading to a relocation of H4K20. In particular, the H4 N-terminal tail interacts with glutamine-76 and aspartate-77 of canonical H3.1 while these interactions are cancelled in the presence of the CENP-A-specific residues valine-76 and lysine-77. Mutations of valine-76 and lysine-77 impair H4K20 monomethylation both in vitro and in vivo. These findings suggest that a CENP-A-mediated structural polymorphism may explain the preferential H4K20 monomethylation in centromeric nucleosomes.

Date: 2019
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DOI: 10.1038/s41467-019-08314-x

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