In methylation, a methyl group (-CH3) is added to position five of the cyto-sine ring in a DNA molecule (see diagram), attaching itself there by means of a chemical bond. For methylation to occur in DNA, certain conditions must be met. The cytosine must be linked to guanine, with the guanine occurring at the 3′ ("three prime") end of the DNA molecule, in a formation that, in scientific notation, is expressed as 5′-CG-3′ and is referred to as a CpG dinucleotide (with the "p" representing a phosphate group). It occurs in many eukaryotic organisms, including mammals, and was recently found to occur in Drosophila (fruit fly), but does not occur in yeast.
The methylation process is performed by enzymes called DNA methyltransferases (DNMTs). Currently, five DNA methyltransferase members have been identified in humans (DNMT1, 2, 3A, 3B, 3L). The precise function of many of these proteins is not yet known. The most well-characterized DNA methyltransferase is DNMT1. This enzyme is required for proper embryonic development in mammals, and is involved in copying the methylation pattern from an existing DNA strand to the newly synthesized DNA strand following DNA replication. For this reason, DNMT1 is called the maintenance DNA methyltransferase. In contrast, DNMT3A and DNMT3B are believed to be de novo methyltransferases, or proteins that can add a methyl group to a cytosine at a new location in the DNA strand, instead of just copying one that already exists. It is not yet known what determines which cytosines in the DNA will have a methyl group added by a de novo methyltransferase.