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

    216 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

    Fingerprint

    Nucleosomes
    Centromere
    Base Pairing
    Histones
    Kinetochores
    DNA
    centromere protein A
    Satellite DNA
    Chromosome Segregation
    Trans-Activators
    Meiosis
    Eukaryota
    Mitosis
    Microtubules
    Chromatin
    Chromosomes
    Binding Sites
    Amino Acids

    ASJC Scopus subject areas

    • General

    Cite this

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

    Crystal structure of the human centromeric nucleosome containing CENP-A. / Tachiwana, Hiroaki; Kagawa, Wataru; Shiga, Tatsuya; Osakabe, Akihisa; Miya, Yuta; Saito, Kengo; Hayashi-Takanaka, Yoko; Oda, Takashi; Sato, Mamoru; Park, Sam Yong; Kimura, Hiroshi; Kurumizaka, Hitoshi.

    In: Nature, Vol. 476, No. 7359, 11.08.2011, p. 232-235.

    Research output: Contribution to journalArticle

    Tachiwana, H, Kagawa, W, Shiga, T, Osakabe, A, Miya, Y, Saito, K, Hayashi-Takanaka, Y, Oda, T, Sato, M, Park, SY, Kimura, H & Kurumizaka, H 2011, 'Crystal structure of the human centromeric nucleosome containing CENP-A', Nature, vol. 476, no. 7359, pp. 232-235. https://doi.org/10.1038/nature10258
    Tachiwana H, Kagawa W, Shiga T, Osakabe A, Miya Y, Saito K et al. Crystal structure of the human centromeric nucleosome containing CENP-A. Nature. 2011 Aug 11;476(7359):232-235. https://doi.org/10.1038/nature10258
    Tachiwana, Hiroaki ; Kagawa, Wataru ; Shiga, Tatsuya ; Osakabe, Akihisa ; Miya, Yuta ; Saito, Kengo ; Hayashi-Takanaka, Yoko ; Oda, Takashi ; Sato, Mamoru ; Park, Sam Yong ; Kimura, Hiroshi ; Kurumizaka, Hitoshi. / Crystal structure of the human centromeric nucleosome containing CENP-A. In: Nature. 2011 ; Vol. 476, No. 7359. pp. 232-235.
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    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.",
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    AU - Saito, Kengo

    AU - Hayashi-Takanaka, Yoko

    AU - Oda, Takashi

    AU - Sato, Mamoru

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