Methylation of DNA at cytosine residues plays an important role in the regulation of gene expression, genomic imprinting, and is essential for mammalian development. Hypermethylation of CpG islands in tumor suppressor genes or hypomethylation of bulk genomic DNA may be linked with development of cancer. To date, three families of mammalian DNA methyltransferase genes have been identified which include DNMT1, DNMT2, and DNMT3. DNMT1 is constitutively expressed in proliferating cells and inactivation of this gene causes global demethylation of genomic DNA and embryonic lethality. DNMT2 is expressed at low levels in adult tissues and its inactivation does not affect DNA methylation or maintenance of methylation. DNMT2 contains all the sequence motifs diagnostic of DNA (cytosine-5)-methyltransferases but appears to lack the large N-terminal regulatory domain common to other eukaryotic methyltransferases.