Regulation of chromatin and gene expression by metabolic enzymes and metabolites

Metabolism and gene expression, which are two fundamental biological processes that are essential to all living organisms, reciprocally regulate each other to maintain homeostasis and regulate cell growth, survival and differentiation. Metabolism feeds into the regulation of gene expression via metabolic enzymes and metabolites, which can modulate chromatin directly or indirectly — through regulation of the activity of chromatin trans-acting proteins, including histone-modifying enzymes, chromatin-remodelling complexes and transcription regulators. Deregulation of these metabolic activities has been implicated in human diseases, prominently including cancer. Metabolism feeds into gene regulation, allowing adaptation of gene expression to satisfy cellular needs, including in pathological scenarios such as cancer. Metabolism modulates gene expression through metabolites, which serve as cofactors for DNA and histone modifiers, and through metabolic enzymes, which locally regulate chromatin and transcription in the nucleus.