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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

06/08/2015

Pubmed ID

26049631

Pubmed Central ID

PMC4479189

DOI

10.1097/MCO.0000000000000188

Scopus ID

2-s2.0-84942800547   33 Citations

Abstract

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 JA

Author

Stephanie Olivier-Van Stichelen PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acetylglucosamine
Alzheimer 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