Specific regulation of epigenome landscape by metabolic enzymes and metabolites

ABSTRACT Metabolism includes anabolism and catabolism, which play an essential role in many biological processes. Chromatin modifications are post‐translational modifications of histones and nucleic acids that play important roles in regulating chromatin‐associated processes such as gene transcription. There is a tight connection between metabolism and chromatin modifications. Many metabolic enzymes and metabolites coordinate cellular activities with alterations in nutrient availability by regulating gene expression through epigenetic mechanisms such as DNA methylation and histone modifications. The dysregulation of gene expression by metabolism and epigenetic modifications may lead to diseases such as diabetes and cancer. Recent studies reveal that metabolic enzymes and metabolites specifically regulate chromatin modifications, including modification types, modification residues and chromatin regions. This specific regulation has been implicated in the development of human diseases, yet the underlying mechanisms are only beginning to be uncovered. In this review, we summarise recent studies of the molecular mechanisms underlying the metabolic regulation of histone and DNA modifications and discuss how they contribute to pathogenesis. We also describe recent developments in technologies used to address the key questions in this field. We hope this will inspire further in‐depth investigations of the specific regulatory mechanisms involved, and most importantly will shed lights on the development of more effective disease therapies.