GlcNAcylation of histone H2B facilitates its monoubiquitination

Ryoji Fujiki, Waka Hashiba, Hiroki Sekine, Atsushi Yokoyama, Toshihiro Chikanishi, Saya Ito, Yuuki Imai, Jaehoon Kim, Housheng Hansen He, Katsuhide Igarashi, Jun Kanno, Fumiaki Ohtake, Hirochika Kitagawa, Robert G. Roeder, Myles Brown, Shigeaki Kato

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

Chromatin reorganization is governed by multiple post-translational modifications of chromosomal proteins and DNA. These histone modifications are reversible, dynamic events that can regulate DNA-driven cellular processes. 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). 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). 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.

Original languageEnglish
Pages (from-to)557-560
Number of pages4
JournalNature
Volume480
Issue number7378
DOIs
Publication statusPublished - 2011 Dec 22
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'GlcNAcylation of histone H2B facilitates its monoubiquitination'. Together they form a unique fingerprint.

  • Cite this

    Fujiki, R., Hashiba, W., Sekine, H., Yokoyama, A., Chikanishi, T., Ito, S., Imai, Y., Kim, J., He, H. H., Igarashi, K., Kanno, J., Ohtake, F., Kitagawa, H., Roeder, R. G., Brown, M., & Kato, S. (2011). GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature, 480(7378), 557-560. https://doi.org/10.1038/nature10656