Cross-talk of Metabolic Pathways and Epigenetic Regulation in Stress Responses

Abstract

Cell-specific gene expression is largely regulated by combinations of DNA-binding transcription factors and various chemical modifications of histone and DNA. Epigenetic regulation is often considered as a stable regulation of gene expression conferred by some of these chemical modifications. Since acetylation of histone and methylation of histone and DNA utilize metabolic intermediates, acetyl-CoA and S-adenosylmethionine (SAM), respectively, it is becoming increasingly appreciated that metabolic status and nutritional conditions affect epigenetic regulation. Methionine adenosyltransferase 2 has recently been shown to form a protein complex with histone methyltransferases and DNA binding transcription factors to regulate genes for oxidative stress response. Conceptually similar complex has been also discovered in yeast cells. Therefore, such protein complexes containing metabolic enzymes may couple metabolism and epigenetic regulation. Recently, undernutrition during embryonic stage has been shown to affect an incident of various diseases in the adult phase, raising the possibility that such conditions alter epigenetic regulation. However, detail epigenetic alterations and mechanisms behind remain still elusive.