You are what you eat: O-linked N-acetylglucosamine in disease, development and epigenetics. Curr Opin Clin Nutr Metab Care 2015 Jul;18(4):339-45
Date
06/08/2015Pubmed ID
26049631Pubmed Central ID
PMC4479189DOI
10.1097/MCO.0000000000000188Scopus ID
2-s2.0-84942800547 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
PURPOSE OF REVIEW: 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.
RECENT FINDINGS: 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.
SUMMARY: 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.
Author List
Olivier-Van Stichelen S, Hanover JAAuthor
Stephanie Olivier-Van Stichelen PhD Associate Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetylglucosamineAlzheimer Disease
Cardiovascular Diseases
Chromatin
Chronic Disease
Diabetes Mellitus, Type 2
Diet
Epigenesis, Genetic
Feeding Behavior
Female
Gene Expression Regulation
Genetic Loci
Genomic Imprinting
Homeostasis
Humans
Hypothalamo-Hypophyseal System
Lupus Erythematosus, Systemic
N-Acetylglucosaminyltransferases
Neoplasms
Neurogenesis
Obesity
Protein Processing, Post-Translational
X Chromosome Inactivation
