DNA Methylation involves the addition of a methyl group to DNA — for example, to the number 5 carbon of the cytosine pyrimidines ring — with the effect of reducing gene expression. DNA Methylation at the 5 position of cytosine has been found in every vertebrate examined. In adult somatic tissues, DNA Methylation typically occurs in a CpG dinucleotide context; non-CpG Methylation is prevalent in embryonic stem cells.

In enzymology, a methylated-DNA-[protein]-cysteine S-methyltransferase (EC 2.1.1.63) is an enzyme that catalyzes the chemical reaction. DNA (containing 6-O-methylguanine) + protein L-cysteine \rightleftharpoons DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine. Thus, the two substrates of this enzyme are DNA containing 6-O-methylguanine and protein L-cysteine, whereas its two products are DNA and protein S-methyl-L-cysteine. The S-methyl-L-cysteine residue irreversibly inactivates the protein, allowing only one transfer for each protein.