Understanding the molecular crosstalk between metabolism and epigenetics

Cellular metabolism has emerged as a central biological node in governing cellular functions. Although previously unappreciated, modulation of the epigenome is now considered intrinsically linked to changes in metabolic activities in the cells. This is particularly the case since both the chemical modifications on histones and DNA, as well as critical co-factors of chromatin enzymes are metabolites which cellular concentrations vary significantly depending on nutrient availability. How and whether specific sub-cellular concentration of metabolites influence chromatin dynamics remains mostly unknown. Similarly, whether the presence of metabolic enzymes in situ at chromatin sites plays important roles in modulating epigenetic modifications has recently been proposed for histone acetylation but remains mostly unexplored for other modifications. On the other hand, epigenetic regulation of metabolic activities in cells has been demonstrated for specific pathways, yet much remains to be explored. In this Research Topic we will attempt to cover the effect of nutrient availability, particularly in different compartments, in modulating chromatin modifications and the activity of chromatin enzymes, in order to direct transcriptional responses as mechanisms to restore metabolic homeostasis. We will also review whether subcellular pools of metabolites shield the epigenetic modulation of gene expression from fluctuations in cytoplasmic metabolite levels. In parallel, we will review the presence of metabolic enzymes in the nucleus and the potential that some of these directly participate in chromatin complexes at sites of modifications.