Graduate School of Frontier Biosciences, Osaka University

Japanese

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

Journal Nat Commun 7, 13465 (2016)
Authors Shang WH (1), Hori T (1), Westhorpe FG (2), Godek KM (3), Toyoda A (4), Misu S (5), Monma N (5), Ikeo K (5), Carroll CW (6), Takami Y (7), Fujiyama A (4, 8), Kimura H (9), Straight AF (2), Fukagawa T (1).
  1. Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
  2. Department of Biochemistry, Stanford University Medical School, 259 Campus Drive, Beckman B409, Stanford, California 94305, USA.
  3. Department of Biochemistry, Geisel School of Medicine, Dartmouth College, HB7200, Hanover, New Hampshire 03755, USA.
  4. Comparative Genomics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  5. -DNA Data Analysis Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  6. Department of Cell Biology, Yale University School of Medicine, SHM C-230, 333 Cedar St., New Haven, Connecticut 06520, USA.
  7. Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
  8. National Institute of Informatics, Hitotsubashi, Chiyoda-ku, Tokyo 101-8430, Japan.
  9. Cell Biology Unit, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Title Acetylation of histone H4 Lysine 5 and 12 is required for CENP-A deposition into centromeres
PubMed 27811920
Laboratory Laboratory of Chromosome Biology 〈Prof. Fukagawa〉
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.