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Modification of Histones by Sugar -N-Acetylglucosamine (GlcNAc) Occurs on Multiple Residues, Including Histone H3 Serine 10, and Is Cell Cycle-regulated
Zhang, S.; Roche, K.; Nasheuer, Heinz-Peter‏; et al.
The monosaccharide, β-N-acetylglucosamine (GlcNAc), can be added to the hydroxyl group of either serines or threonines to generate an O-linked β-N-acetylglucosamine (O-GlcNAc) residue (Love, D. C., and Hanover, J. A. (2005) Sci. STKE 2005 312, 1–14; Hart, G. W., Housley, M. P., and Slawson, C. (2007) Nature 446, 1017–1022). This post-translational protein modification, termed O-GlcNAcylation, is reversible, analogous to phosphorylation, and has been implicated in many cellular processes. Here, we present evidence that in human cells all four core histones of the nucleosome are substrates for this glycosylation in the relative abundance H3, H4/H2B, and H2A. Increasing the intracellular level of UDP-GlcNAc, the nucleotide sugar donor substrate for O-GlcNAcylation enhanced histone O-GlcNAcylation and partially suppressed phosphorylation of histone H3 at serine 10 (H3S10ph). Expression of recombinant H3.3 harboring an S10A mutation abrogated histone H3 O-GlcNAcylation relative to its wild-type version, consistent with H3S10 being a site of histone O-GlcNAcylation (H3S10glc). Moreover, O-GlcNAcylated histones were lost from H3S10ph immunoprecipitates, whereas immunoprecipitation of either H3K4me3 or H3K9me3 (active or inactive histone marks, respectively) resulted in co-immunoprecipitation of O-GlcNAcylated histones. We also examined histone O-GlcNAcylation during cell cycle progression. Histone O-GlcNAcylation is high in G1 cells, declines throughout the S phase, increases again during late S/early G2, and persists through late G2 and mitosis. Thus, O-GlcNAcylation is a novel histone post-translational modification regulating chromatin conformation during transcription and cell cycle progression. (SFI) Principal Investigator award (07/IN1/B958) and a Health Research Board (HRB) Project Grant (RP/2005/265) (to N. F. L.). Deposited by bulk import
Keyword(s): Cell Cycle; Chromatin Modification; Glycosylation; Histone Modification; Histones; Phosphorylation; O-GlcNAcylation
Publication Date:
2013
Type: Journal article
Peer-Reviewed: Unknown
Language(s): English
Institution: University College Dublin
Publisher(s): American Society for Biochemistry and Molecular Biology
First Indexed: 2015-02-04 05:43:08 Last Updated: 2018-10-11 16:42:40