Title :
GlcNAcylation of
histone H2B facilitates its monoubiquitination
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 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