INTERPLAY OF HISTONE ACETYLTRANSFERASES WITH CELLULAR METABOLISM
Histone modifying enzymes are responsive to changes in cellular metabolism because these epigenetic modifiers use sentinel metabolites as co-factors, i.e. histone methyltransferases (HMTs) use S-adenosylmethionine (SAM), while histone acetylatransferases (HATs) use acetyl-coenzyme A (acetyl-coA). Consequently, it is important to understand how epigenetic mechanisms and cellular metabolism cross-regulate each other. It has already been appreciated that the epigenetic machinery
impacts on metabolism through transcriptional control of key metabolic genes. Alternatively, histone post-translational modifiers may have a direct impact on metabolism by modulating intracellular metabolite levels since they are major consumers of these intermediary molecules. Using our expertise in histone modifications and employing metabolomics approaches we are interested to determine whether altering the activity of histone acetyltransferases by environmental or genetic perturbations would consequently change the consumption of acetyl-coA by histones and would this then induce cellular metabolic rewiring.
Acetyl-CoA is a central metabolic intermediate because it is found at the intersection of many metabolic pathways. Therefore, its availability and rate of consumption can directly influence the epigenome through histone acetylation and other metabolic states of a cell.