Metabolism produces the energy necessary for various cellular processes. An imbalance between energy intake and expenditure results in the accumulation of nutrients and metabolites, ultimately leading to metabolic diseases. To avoid this, cells constantly are adjusting their metabolic state based on nutrient availability, using extracellular signaling driven by growth factors, hormones, or cytokines. An important feature of metabolic control is the transcriptional regulation of rate-limiting metabolic enzymes, which usually involves epigenetic mechanisms. The ad hoc levels of metabolites, such as NAD+, adenine triphosphate (ATP), acetyl-CoA, and S-adenosylmethionine (SAM), and of metabolic hormones such as insulin and leptin, contribute to the temporal control of gene expression. The activities of enzymes involved in epigenetic modifications, such as DNA methyl-transferases (DNMTs), histone acetyltransferases (HATs), HDACs, histone methyltransferases (HMTs), and histone demethylases (HDMs), are regulated, in part, by the concentrations of their required substrates and cofactors (Lee and Workman 2007). Thus, the cell’s metabolic state is tightly integrated in the epigenome and transcriptional regulation.
