Crystal structure of the human centromeric nucleosome containing CENP-A

Hiroaki Tachiwana, Wataru Kagawa, Tatsuya Shiga, Akihisa Osakabe, Yuta Miya, Kengo Saito, Yoko Hayashi-Takanaka, Takashi Oda, Mamoru Sato, Sam Yong Park, Hiroshi Kimura, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    225 Citations (Scopus)

    Abstract

    In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment. Centromeres specify the kinetochore formation sites on individual chromosomes, and are epigenetically marked by the assembly of nucleosomes containing the centromere-specific histone H3 variant, CENP-A. Although the underlying mechanism is unclear, centromere inheritance is probably dictated by the architecture of the centromeric nucleosome. Here we report the crystal structure of the human centromeric nucleosome containing CENP-A and its cognate ±-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome, the DNA is wrapped around the histone octamer, consisting of two each of histones H2A, H2B, H4 and CENP-A, in a left-handed orientation. However, unlike the canonical H3 nucleosome, only the central 121 base pairs of the DNA are visible. The thirteen base pairs from both ends of the DNA are invisible in the crystal structure, and the ±N helix of CENP-A is shorter than that of H3, which is known to be important for the orientation of the DNA ends in the canonical H3 nucleosome. A structural comparison of the CENP-A and H3 nucleosomes revealed that CENP-A contains two extra amino acid residues (Arg 80 and Gly 81) in the loop 1 region, which is completely exposed to the solvent. Mutations of the CENP-A loop 1 residues reduced CENP-A retention at the centromeres in human cells. Therefore, the CENP-A loop 1 may function in stabilizing the centromeric chromatin containing CENP-A, possibly by providing a binding site for trans-acting factors. The structure provides the first atomic-resolution picture of the centromere-specific nucleosome.

    Original languageEnglish
    Pages (from-to)232-235
    Number of pages4
    JournalNature
    Volume476
    Issue number7359
    DOIs
    Publication statusPublished - 2011 Aug 11

    ASJC Scopus subject areas

    • General

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    Tachiwana, H., Kagawa, W., Shiga, T., Osakabe, A., Miya, Y., Saito, K., Hayashi-Takanaka, Y., Oda, T., Sato, M., Park, S. Y., Kimura, H., & Kurumizaka, H. (2011). Crystal structure of the human centromeric nucleosome containing CENP-A. Nature, 476(7359), 232-235. https://doi.org/10.1038/nature10258