Gene Regulation and Cellular Metabolism: An Essential Partnership.

It is recognized that cell metabolism is tightly connected to other cellular processes such as regulation of gene expression. Metabolic pathways not only provide the precursor molecules necessary for gene expression, but they also provide ATP, the primary fuel driving gene expression. However, metabolic conditions are highly variable since nutrient uptake is not a uniform process. Thus, cells must continually calibrate gene expression to their changing metabolite and energy budgets. This review discusses recent advances in understanding the molecular and biophysical mechanisms that connect metabolism and gene regulation as cells navigate their growth, proliferation, and differentiation. Particular focus is given to these mechanisms in the context of organismal development. Gene expression may only account for 10% of a cell's energy budget, which undergoes complete ATP turnover every minute. Multilayered feedback repression enables gene expression to adapt to variable metabolic rates. Energy expenditure via nucleosome displacement and modification regulates transcription factor accessibility and ultrasensitivity. Aerobic glycolysis versus oxidative phosphorylation have distinct effects on epigenetic modifications. [ABSTRACT FROM AUTHOR]