Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation Levels.

Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood but could alter gene expression and influence metabolic health. ATP citrate-lyase produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types.

ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch.

Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY), cells remain viable and proliferate, although at an impaired rate.

Metabolism and epigenetics: a link cancer cells exploit.

Both cellular nutrient metabolism and chromatin organization are remodeled in cancer cells, and these alterations play key roles in tumor development and growth. Many chromatin modifying-enzymes utilize metabolic intermediates as cofactors or substrates, and recent studies have demonstrated that the epigenome is sensitive to cellular metabolism. The contribution of metabolic alterations to epigenetic deregulation in cancer cells is just beginning to emerge, as are the roles of the metabolism-epigenetics link in tumorigenesis.