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Acetylation of histone H4 lysine 5 and 12 is required for CENP-A deposition into centromeres

Author

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  • Wei-Hao Shang

    (Graduate School of Frontier Biosciences, Osaka University)

  • Tetsuya Hori

    (Graduate School of Frontier Biosciences, Osaka University)

  • Frederick G. Westhorpe

    (Stanford University Medical School)

  • Kristina M. Godek

    (Geisel School of Medicine, Dartmouth College)

  • Atsushi Toyoda

    (Comparative Genomics Laboratory, National Institute of Genetics)

  • Sadahiko Misu

    (DNA Data Analysis Laboratory, National Institute of Genetics)

  • Norikazu Monma

    (DNA Data Analysis Laboratory, National Institute of Genetics)

  • Kazuho Ikeo

    (DNA Data Analysis Laboratory, National Institute of Genetics)

  • Christopher W. Carroll

    (Yale University School of Medicine)

  • Yasunari Takami

    (Section of Biochemistry and Molecular Biology, University of Miyazaki)

  • Asao Fujiyama

    (Comparative Genomics Laboratory, National Institute of Genetics
    National Institute of Informatics, Hitotsubashi)

  • Hiroshi Kimura

    (Cell Biology Unit, Institute of Innovative Research, Tokyo Institute of Technology)

  • Aaron F. Straight

    (Stanford University Medical School)

  • Tatsuo Fukagawa

    (Graduate School of Frontier Biosciences, Osaka University)

Abstract

Centromeres are specified epigenetically through the deposition of the centromere-specific histone H3 variant CENP-A. However, how additional epigenetic features are involved in centromere specification is unknown. Here, we find that histone H4 Lys5 and Lys12 acetylation (H4K5ac and H4K12ac) primarily occur within the pre-nucleosomal CENP-A–H4–HJURP (CENP-A chaperone) complex, before centromere deposition. We show that H4K5ac and H4K12ac are mediated by the RbAp46/48–Hat1 complex and that RbAp48-deficient DT40 cells fail to recruit HJURP to centromeres and do not incorporate new CENP-A at centromeres. However, C-terminally-truncated HJURP, that does not bind CENP-A, does localize to centromeres in RbAp48-deficient cells. Acetylation-dead H4 mutations cause mis-localization of the CENP-A–H4 complex to non-centromeric chromatin. Crucially, CENP-A with acetylation-mimetic H4 was assembled specifically into centromeres even in RbAp48-deficient DT40 cells. We conclude that H4K5ac and H4K12ac, mediated by RbAp46/48, facilitates efficient CENP-A deposition into centromeres.

Suggested Citation

  • Wei-Hao Shang & Tetsuya Hori & Frederick G. Westhorpe & Kristina M. Godek & Atsushi Toyoda & Sadahiko Misu & Norikazu Monma & Kazuho Ikeo & Christopher W. Carroll & Yasunari Takami & Asao Fujiyama & H, 2016. "Acetylation of histone H4 lysine 5 and 12 is required for CENP-A deposition into centromeres," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13465
    DOI: 10.1038/ncomms13465
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