Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes

Abstract

The physiological identity of every cell is maintained by highly specific transcriptional networks that establish a coherent molecular program that is in-tune with nutritional conditions. The regulation of cell-specific transcriptional networks is accomplished by an epigenetic program via chromatin modifying enzymes, whose activity is directly dependent on metabolites such as acetyl-CoA, S-adenosylmethionine and NAD+ among others. Therefore, these nuclear activities are directly influenced by the nutritional status of the cell. In addition to nutritional availability, this highly collaborative program between epigenetic dynamics and metabolism is further interconnected with other environmental cues provided by the day-night cycles imposed by circadian rhythms. Herein, we review molecular pathways and their metabolites associated with epigenetic adaptations modulated by histone- and DNA-modifying enzymes and their responsiveness to the environment in the context of health and disease.

The impact of cellular metabolism on chromatin dynamics and epigenetics

“…Some examples which are non-exhaustive and have been reviewed extensively elsewhere 7–9, 17, 25, 32–38 include histone methyltransferases, glycosyltransferases, demethylases, acetyltransferases, deacetylases, deacylases, DNA and RNA methyltransferases and demethylases. As has been reviewed extensively 3, 9, 19, 28, 30, 31, 39–44 , these enzymes utilize, as substrates and cofactors, metabolites derived from diverse metabolic pathways including serine-glycine one carbon (SGOC) metabolism and particularly the methionine cycle, the tricarboxylic acid cycle, beta oxidation, glycolysis, and hexosamine biosynthesis. In these metabolic networks, intermediate metabolites including S-adenosylmethionine (SAM), Acetyl-coenzyme A (Acetyl-CoA), NAD + , alpha-ketoglutarate (αKG), and Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), and others, serve as substrates for enzymes that modify chromatin and nucleic acids.…”

Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

“…Energy-generating pathways are highly dynamic and metabolic fluxes vary dramatically across different cell types and tissues in response to developmental signals [6], nutritional status [7], environmental signals [8] and disease pathogenesis [9]. Metabolic flux is finely tuned to maximize function in different cell types and is linked to cell identity just as gene expression, epigenetics and morphology are.…”

Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation Levels

“…acetyl-CoA is the acetyl group donor for acetylation, whereas the methyl donor S-adenosylmethionine is required for methylation) (5)(6)(7)(8)(9). Although the connection between cell metabolism and chromatin modification has been documented in numerous studies using model organisms, mammalian cell culture systems, and cancer models (5-9), whether diet influences chromatin modifications in different tissues remains poorly understood.…”