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

Author

Listed:
  • Yasuhiro Arimura

    (The University of Tokyo
    Waseda University)

  • Hiroaki Tachiwana

    (Waseda University
    The Cancer Institute of Japanese Foundation for Cancer Research)

  • Hiroki Takagi

    (The University of Tokyo
    Waseda University)

  • Tetsuya Hori

    (Osaka University)

  • Hiroshi Kimura

    (Tokyo Institute of Technology)

  • Tatsuo Fukagawa

    (Osaka University)

  • Hitoshi Kurumizaka

    (The University of Tokyo
    Waseda University)

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.

Suggested Citation

  • Yasuhiro Arimura & Hiroaki Tachiwana & Hiroki Takagi & Tetsuya Hori & Hiroshi Kimura & Tatsuo Fukagawa & Hitoshi Kurumizaka, 2019. "The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08314-x
    DOI: 10.1038/s41467-019-08314-x
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    Cited by:

    1. Natalia Pardo-Lorente & Anestis Gkanogiannis & Luca Cozzuto & Antoni Gañez Zapater & Lorena Espinar & Ritobrata Ghose & Jacqueline Severino & Laura García-López & Rabia Gül Aydin & Laura Martin & Mari, 2024. "Nuclear localization of MTHFD2 is required for correct mitosis progression," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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