The epigenomic impact of methylation in metabolic dysfunction and cancer

Abstract The term “epigenetics” refers to heritable changes in gene expression and cellular phenotype that do not involve changes to the genetic code. Epigenetic changes include DNA methylation, histone modifications and nucleosome positioning that alter chromatin structure. Epigenetic marks can be influenced by environmental cues, changes in nutrient availability and the emergence of mutations in metabolic enzymes or oncogenes that alter metabolism and can act as a metabolic switch to alter DNA methylation, chromatin remodeling and consequently, changes in gene expression. In this chapter we will focus on four questions: (1) What is DNA methylation and its role in regulating gene expression; (2) Which enzymes, substrates and cofactors are important for DNA methylation and how are these influenced by metabolism, (3) How does the loss or gain of DNA methylation impact metabolism; (4) How do mutations in tumor suppressors alter DNA methylation and regulate metabolism.