LAUSR

The nuclear metabolic-epigenetic axis bridges the environment and genes to modulate behavior To drive behaviors essential for survival, numerous pathways have evolved that translate environmental stimuli into gene expression. These include interactions between metabolic and epigenetic regulation, which encompass both predictable indirect connections and unanticipated direct contacts (1). Indirect pathways involve metabolites generated from diet and other sources that provide substrates and cofactors for epigenetic enzymes to ensure seamless adaption to nutrient availability. In addition, epigenetic mechanisms regulate the expression of metabolic enzymes, which can in turn produce or deplete various metabolites. The direct metabolic-epigenetic interface, however, represents a paradigm shift in our mechanistic understanding of environmental impacts on gene expression and behavior. Direct communication is mediated by metabolic enzymes—classically thought to reside in mitochondria and cytoplasm—localizing within the nucleus and even binding to chromatin. This surprising relocation enables the generation of metabolite pools that can fuel epigenetic enzymes directly.