title: You are what you eat: O-linked N-acetylglucosamine in disease, development and epigenetics.
abstract: OBJECTIVE
  The O-linked N-acetylglucosamine (O-GlcNAc) modification is both responsive to nutrient availability and capable of altering intracellular cellular signalling. We summarize data defining a role for O-GlcNAcylation in metabolic homeostasis and epigenetic regulation of development in the intrauterine environment.
  
  
  RESULTS
  O-GlcNAc transferase (OGT) catalyzes nutrient-driven O-GlcNAc addition and is subject to random X-inactivation. OGT plays key roles in growth factor signalling, stem cell biology, epigenetics and possibly imprinting. The O-GlcNAcase, which removes O-GlcNAc, is subject to tight regulation by higher order chromatin structure. O-GlcNAc cycling plays an important role in the intrauterine environment wherein OGT expression is an important biomarker of placental stress.
  
  
  CONCLUSIONS
  Regulation of O-GlcNAc cycling by X-inactivation, epigenetic regulation and nutrient-driven processes makes it an ideal candidate for a nutrient-dependent epigenetic regulator of human disease. In addition, O-GlcNAc cycling influences chromatin modifiers critical to the regulation and timing of normal development including the polycomb repression complex and the ten-eleven translocation proteins mediating DNA methyl cytosine demethylation. The pathway also impacts the hypothalamic-pituitary-adrenal axis critical to intrauterine programming influencing disease susceptibility in later life.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland, USA.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Olivier-Van Stichelen
authors.forename: John A
authors.initials: JA
authors.lastname: Hanover
mesh_terms: D000117:Acetylglucosamine / Q000008:administration & dosage* / Q000009:adverse effects*; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics; D004032:Diet; D044127:Epigenesis, Genetic; D005247:Feeding Behavior; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D018392:Genomic Imprinting; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D055495:Neurogenesis / Q000187:drug effects; D009765:Obesity / Q000209:etiology / Q000235:genetics; D011499:Protein Processing, Post-Translational; D049951:X Chromosome Inactivation / Q000502:physiology
chemical_list: D002843:Chromatin; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D000117:Acetylglucosamine