Nap1 regulates proper CENP-B binding to nucleosomes

Hiroaki Tachiwana, Yuta Miya, Nobuaki Shono, Jun Ichirou Ohzeki, Akihisa Osakabe, Koichiro Otake, Vladimir Larionov, William C. Earnshaw, Hiroshi Kimura, Hiroshi Masumoto, Hitoshi Kurumizaka

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    11 Citations (Scopus)

    Abstract

    CENP-B is a widely conserved centromeric satellite DNA-binding protein, which specifically binds to a 17-bp DNA sequence known as the CENP-B box. CENP-B functions positively in the de novo assembly of centromeric nucleosomes, containing the centromere-specific histone H3 variant, CENPA. At the same time, CENP-B also prevents undesired assembly of the CENP-A nucleosome through heterochromatin formation on satellite DNA integrated into ectopic sites. Therefore, improper CENP-B binding to chromosomes could be harmful. However, no CENP-B eviction mechanism has yet been reported. In the present study, we found that human Nap1, an acidic histone chaperone, inhibited the non-specific binding of CENP-B to nucleosomes and apparently stimulated CENP-B binding to its cognate CENP-B box DNA in nucleosomes. In human cells, the CENP-B eviction activity of Nap1 was confirmed in model experiments, in which the CENP-B binding to a human artificial chromosome or an ectopic chromosome locus bearing CENP-B boxes was significantly decreased when Nap1 was tethered near the CENP-B box sequence. In contrast, another acidic histone chaperone, sNASP, did not promote CENP-B eviction in vitro and in vivo and did not stimulate specific CENP-B binding to CENP-A nucleosomes in vitro. We therefore propose a novel mechanism of CENP-B regulation by Nap1.

    Original languageEnglish
    Pages (from-to)2869-2880
    Number of pages12
    JournalNucleic Acids Research
    Volume41
    Issue number5
    DOIs
    Publication statusPublished - 2013 Mar

    ASJC Scopus subject areas

    • Genetics

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  • Cite this

    Tachiwana, H., Miya, Y., Shono, N., Ohzeki, J. I., Osakabe, A., Otake, K., Larionov, V., Earnshaw, W. C., Kimura, H., Masumoto, H., & Kurumizaka, H. (2013). Nap1 regulates proper CENP-B binding to nucleosomes. Nucleic Acids Research, 41(5), 2869-2880. https://doi.org/10.1093/nar/gks1464