Acetylation of histone H4 Lysine 5 and 12 is required for CENP-A deposition into centromeres
Journal | Nat Commun 7, 13465 (2016) |
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Title | Acetylation of histone H4 Lysine 5 and 12 is required for CENP-A deposition into centromeres |
Laboratory | Laboratory of Chromosome Biology〈Prof. FUKAGAWA Tatsuo〉 |
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.
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)
Abstract |
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PubMed | 27811920 |