GlcNAcylation of histone H2B facilitates its monoubiquitination

• Published in: Nature (London) Vol. 480; no. 7378; pp. 557 - 560
• Main Authors: Fujiki, Ryoji, Hashiba, Waka, Sekine, Hiroki, Yokoyama, Atsushi, Chikanishi, Toshihiro, Ito, Saya, Imai, Yuuki, Kim, Jaehoon, He, Housheng Hansen, Igarashi, Katsuhide, Kanno, Jun, Ohtake, Fumiaki, Kitagawa, Hirochika, Roeder, Robert G., Brown, Myles, Kato, Shigeaki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.12.2011; Nature Publishing Group
• Subjects: 631/337/100/2285; 631/80/458/582; 631/80/474/2073; Acetylglucosamine - metabolism; Amino Acid Sequence; Animals; Biological and medical sciences; Cell Line; Chemical properties; Chromatin. Chromosome; Chromosomal proteins; Fundamental and applied biological sciences. Psychology; Glucose metabolism; HeLa Cells; Histones; Histones - chemistry; Histones - genetics; Histones - metabolism; Humanities and Social Sciences; Humans; letter; Models, Molecular; Molecular and cellular biology; Molecular genetics; multidisciplinary; Mutation; Physiological aspects; Protein Structure, Tertiary; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Science; Science (multidisciplinary); Ubiquitination; Japan; Posttranslational modification; Cell component; Chromatin; Histone H2B; Organization
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature10656

Genome-wide analysis shows that H2B S112 O -linked to N -acetylglucosamine is frequently located near transcribed genes, suggesting that histone GlcNAcylation facilitates transcription of the genes. Histone H2B glycosylation Post-translational histone modification can be important in transcriptional regulation. Here, histone H2B is shown to be modified by the addition of O -linked N -acetylglucosamine ( O -GlcNAc) in response to extracellular glucose. GlcNAcylation of H2B at Ser112 facilitates monoubiquitylation of the histone at Lys120. H2B ubiquitylation has been previously implicated in active transcription. GlcNAcylation of H2B may facilitate gene expression in response to glucose availability. Chromatin reorganization is governed by multiple post-translational modifications of chromosomal proteins and DNA 1 , 2 . These histone modifications are reversible, dynamic events that can regulate DNA-driven cellular processes 3 , 4 . However, the molecular mechanisms that coordinate histone modification patterns remain largely unknown. In metazoans, reversible protein modification by O -linked N -acetylglucosamine (GlcNAc) is catalysed by two enzymes, O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA) 5 , 6 . However, the significance of GlcNAcylation in chromatin reorganization remains elusive. Here we report that histone H2B is GlcNAcylated at residue S112 by OGT in vitro and in living cells. Histone GlcNAcylation fluctuated in response to extracellular glucose through the hexosamine biosynthesis pathway (HBP) 5 , 6 . H2B S112 GlcNAcylation promotes K120 monoubiquitination, in which the GlcNAc moiety can serve as an anchor for a histone H2B ubiquitin ligase. H2B S112 GlcNAc was localized to euchromatic areas on fly polytene chromosomes. In a genome-wide analysis, H2B S112 GlcNAcylation sites were observed widely distributed over chromosomes including transcribed gene loci, with some sites co-localizing with H2B K120 monoubiquitination. These findings suggest that H2B S112 GlcNAcylation is a histone modification that facilitates H2BK120 monoubiquitination, presumably for transcriptional activation.