Chapter 17 - Metabolic Regulation of DNA Methylation in Mammals

Abstract

This chapter focuses on the metabolic processes involved in one-carbon (methyl) donor production and their impact on DNA methylation. It discusses the metabolic regulation of DNA methylation in mammals. More than 100 methyltransferase enzymes (including four DNA methyltransferases) have been described in mammals, involved in the transfer of methyl groups to a large array of proteins, phospholipids, and nucleotides. These reactions are fundamental to many different cellular functions, and it is therefore not surprising that insufficient methyl donor availability has the potential to disrupt a wide variety of biological processes, including DNA nucleotide synthesis and methylation, and gene expression (among others). The production of sufficient methyl-donors is therefore of critical importance for faithful cell division and development. The methylated maternal and paternal genomes are de-methylated at fertilization and specific patterns of methylation are then re-established progressively starting in the early post-conception period. The methyl groups required for establishment and maintenance of DNA methylation are derived solely from dietary methyl donors in association with specific enzymes and associated cofactors. The metabolic pathways that generate the primary methyl donors needed for the de novo establishment and maintenance of the DNA methylation profile are complicated and do not exist in isolation from other essential biochemical reactions necessary for cell survival, division, and differentiation.