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Nat Commun. 2016 Nov 4;7:13465. doi: 10.1038/ncomms13465.

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

Author information

  • 1Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
  • 2Department of Biochemistry, Stanford University Medical School, 259 Campus Drive, Beckman B409, Stanford, California 94305, USA.
  • 3Department of Biochemistry, Geisel School of Medicine, Dartmouth College, HB7200, Hanover, New Hampshire 03755, USA.
  • 4Comparative Genomics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  • 5DNA Data Analysis Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  • 6Department of Cell Biology, Yale University School of Medicine, SHM C-230, 333 Cedar St., New Haven, Connecticut 06520, USA.
  • 7Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
  • 8National Institute of Informatics, Hitotsubashi, Chiyoda-ku, Tokyo 101-8430, Japan.
  • 9Cell Biology Unit, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.

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.

PMID:
27811920
PMCID:
PMC5097169
DOI:
10.1038/ncomms13465
[PubMed - in process]
Free PMC Article
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