Cancer cells are characterized by major alterations in both cellular metabolism and epigenetic profiles. Current understanding of links between metabolism and chromatin in the context of cancer is currently very limited. We have previously demonstrated that acetylation of histones is sensitive to glucose availability through the enzyme ATP-citrate lyase (ACL), which produces acetyl-CoA from citrate. While this is likely to impact gene expression and other chromatin-dependent processes, the molecular mechanisms and functional significance of metabolic regulation of lysine acetylation are poorly understood. In this presentation, I will focus on current efforts to elucidate how metabolic signals are conveyed to chromatin. I will also discuss recent findings demonstrating a novel link between ACL and another chromatin-modifying enzyme, DNA methyltransferase 1, during adipocyte differentiation. Learning Objectives: Understand how changes in cellular metabolism impact chromatin modifications such as histone acetylation. Learn about the role of ATP-citrate lyase in regulating gene expression and epigenetics during adipocyte differentiation.