DNA methylation, a key component of genetic regulation, occurs primarily at the 5-carbon of the base cytosine, forming 5’methylcytosine (see left). Methylation is an epigenetic modification catalyzed by DNA methyltransferase enzymes, including DNMT1, DNMT2, and DNMT3. These enzymes use S-adenosylmethionine as a methyl donor and contain several highly conserved structural features between the three forms; these include the S-adenosylmethionine binding site, a vicinal proline-cysteine pair which forms a thiolate anion important for the reaction mechanism, and the cytosine substrate binding pocket. Many features of DNA methyltransferases are highly conserved throughout many classes of life, from bacteria to mammals. In addition to controlling the expression of certain genes, there are a variety of protein complexes, many with implications for human health, which only bind to methylated DNA recognition sites. Many of the early DNA methyltransferases have been thought to be derived from RNA methyltransferases that were supposed to be active in the RNA world to protect many species of primitive RNA.