Bittersweet memories: linking metabolism to epigenetics through O-GlcNAcylation

Nat Rev Mol Cell Biol. 2012 Apr 23;13(5):312-21. doi: 10.1038/nrm3334.


O-GlcNAcylation, which is a nutrient-sensitive sugar modification, participates in the epigenetic regulation of gene expression. The enzymes involved in O-linked β-D-N-acetylglucosamine (O-GlcNAc) cycling - O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) - target key transcriptional and epigenetic regulators including RNA polymerase II, histones, histone deacetylase complexes and members of the Polycomb and Trithorax groups. Thus, O-GlcNAc cycling may serve as a homeostatic mechanism linking nutrient availability to higher-order chromatin organization. In response to nutrient availability, O-GlcNAcylation is poised to influence X chromosome inactivation and genetic imprinting, as well as embryonic development. The wide range of physiological functions regulated by O-GlcNAc cycling suggests an unexplored nexus between epigenetic regulation in disease and nutrient availability.

Publication types

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

MeSH terms

  • Acetylglucosamine / metabolism*
  • Acetylglucosaminidase / chemistry
  • Acetylglucosaminidase / metabolism
  • Acetylglucosaminidase / physiology
  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism
  • Epigenesis, Genetic*
  • Glycosylation
  • Humans
  • Metabolic Networks and Pathways
  • N-Acetylgalactosaminyltransferases / chemistry
  • N-Acetylgalactosaminyltransferases / metabolism
  • N-Acetylgalactosaminyltransferases / physiology
  • Nutritional Status / genetics*
  • Protein Conformation
  • Protein Processing, Post-Translational*


  • Chromatin
  • N-Acetylgalactosaminyltransferases
  • Acetylglucosaminidase
  • Acetylglucosamine