O-GlcNAc and the epigenetic regulation of gene expression

J Biol Chem. 2014 Dec 12;289(50):34440-8. doi: 10.1074/jbc.R114.595439. Epub 2014 Oct 21.

Abstract

O-GlcNAcylation is an abundant nutrient-driven modification linked to cellular signaling and regulation of gene expression. Utilizing precursors derived from metabolic flux, O-GlcNAc functions as a homeostatic regulator. The enzymes of O-GlcNAc cycling, OGT and O-GlcNAcase, act in mitochondria, the cytoplasm, and the nucleus in association with epigenetic "writers" and "erasers" of the histone code. Both O-GlcNAc and O-phosphate modify repeats within the RNA polymerase II C-terminal domain (CTD). By communicating with the histone and CTD codes, O-GlcNAc cycling provides a link between cellular metabolic status and the epigenetic machinery. Thus, O-GlcNAcylation is poised to influence trans-generational epigenetic inheritance.

Keywords: Epigenetics; Glycobiology; Histones; O-GlcNAc; O-GlcNAcylation; Polycomb; RNA Polymerase II; Signaling; Transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Acetylglucosamine / metabolism*
  • Animals
  • Epigenesis, Genetic*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • N-Acetylglucosaminyltransferases / metabolism
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • Histones
  • N-Acetylglucosaminyltransferases
  • RNA Polymerase II
  • hexosaminidase C
  • beta-N-Acetylhexosaminidases
  • Acetylglucosamine