Nutrient regulation of gene expression by O-GlcNAcylation of chromatin

Abstract

O-GlcNAcylation is a dynamic post-translational modification that is responsive to nutrient availably via the hexosamine biosynthetic pathway and its endproduct UDP-GlcNAc. O-GlcNAcylation serves as a nutrient sensor to regulate the activities of many proteins involved in nearly all biological processes. Within the last decade, OGT, OGA and O-GlcNAcylation have been shown to be at the nexus of epigenetic marks controlling gene expression during embryonic development, cell differentiation, in the maintenance of epigenetic states and in the etiology of epigenetic related diseases. OGT O-GlcNAcylates histones and epigenetic writers/erasers, and regulates gene activation, as well as gene repression. Here, we highlight recent work documenting the important roles O-GlcNAcylation and its cycling enzymes play in the nutrient regulation of epigenetic partners controlling gene expression.

Nutriepigenomics Advances into Personalized Nutrition

“…More recently, in a double-bind, randomized cross-over trial in menopausal women isoflavones affected in peripheral blood mononuclear cells the expression of 357 genes which are involved in inflammation, oxidative phosphorylation and cell cycle have been published up to now describing the genomic impact of polyphenols and polyphenol-rich foods in humans. It has been observed that the daily intake of 150 mg quercetin for 2 weeks significantly affected the expression of 788 genes in CD14-positivemonocytes, genes related to immune system, apoptosis or cell signaling pathways [16].…”

“…This potential cardiovascular health benefit is in agreement with a recent study that showed an association between the intake of flavanols and reduced risk of coronary heart diseases. However, comprehensive understanding of the biological activity of flavanols including their mechanisms of action in humans is still enigmatic [16]. The gene expression profile of blood leukocytes was obtained following 8 weeks consumption of MOF.…”

“…Statistical analyses revealed 864differentially expressed genes (p.0.05 and corrected p,0.1). Out of the 864 genes, 445 were identified as down regulated and 419 as up-regulated, with expression changes varying from 1.32 to 1.72 [16]. To identify the biological function in which these genes are involved, gene ontology, pathway and gene network analyses were performed.…”

“…Among the identified transcription factors are SP1, p53, AP1 and NF-kB. A network of genes centred to NF-kB and affected by the MOFsupplementation is presented in (Figure 4) [16].…”

The O‐GlcNAc transferase OGT interacts with and post‐translationally modifies the transcription factor HOXA1

“…O‐GlcNAc adducts are also present on histone proteins indicating OGT contributes to modulate epigenetic regulatory landscapes . OGT interacts with other chromatin modification proteins and transcriptional regulators, like TET proteins (mediate the 5 hydroxy‐methylation of cytosines, 5hmC), HCF1 (promotes histone H3 lysine 4 trimethylation, H3K4me3), MLL5 (catalyses H3K4 mono‐and di‐methylation, H3K4me1/2) and Polycomb proteins (contribute to H2BK119 ubiquitination and H3K27 trimethlyation, H3K27me3) . Finally, transcription factors themselves can be modified by OGT.…”