O-GlcNAcylation, an Epigenetic Mark. Focus on the Histone Code, TET Family Proteins, and Polycomb Group Proteins

Abstract

There are increasing evidences that dietary components and metabolic disorders affect gene expression through epigenetic mechanisms. These observations support the notion that epigenetic reprograming-linked nutrition is connected to the etiology of metabolic diseases and cancer. During the last 5 years, accumulating data revealed that the nutrient-sensing O-GlcNAc glycosylation (O-GlcNAcylation) may be pivotal in the modulation of chromatin remodeling and in the regulation of gene expression by being part of the “histone code,” and by identifying OGT (O-GlcNAc transferase) as an interacting partner of the TET family proteins of DNA hydroxylases and as a member of the polycomb group proteins. Thus, it is suggested that O-GlcNAcylation is a post-translational modification that links nutrition to epigenetic. This review summarizes recent findings about the interplay between O-GlcNAcylation and the epigenome and enlightens the contribution of the glycosylation to epigenetic reprograming.

Proteolysis of HCF-1 by Ser/Thr glycosylation-incompetent O-GlcNAc transferase:UDP-GlcNAc complexes

“…As UDP-GlcNAc is produced by the nutrient-dependent hexosamine biosynthetic pathway (Hart et al 2011), it has been suggested that O-GlcNAcylation by the OGT:UDP-GlcNAc complex serves as a nutrient sensor to regulate such processes as gene expression (see Dehennaut et al 2014).…”

The omniscient placenta: Metabolic and epigenetic regulation of fetal programming

“…As nutrient transfer in the placenta from maternal sources to the developing fetus is of paramount importance, placental OGT affectively serves as a molecular “canary in a coal mine”, sensing changes in maternal energy and altering placental signaling to ultimately impact fetal programing. Recently, OGT’s domain has been expanded to epigenetics with the discovery that O-GlcNAclyation regulates several critical epigenetic links, including DNA demethylases and histone marks (reviewed by Dehennaut, Leprince, & Lefebvre, 2014). …”

Nutriepigenomics Advances into Personalized Nutrition

“…These eight PPL-associatedmethylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by a previous GWAS (4.5%). In summary, the epigenomeis a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD [3,6,[13][14][15].…”