Methylation of DNA at cytosine residues plays an important role in 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. DNMT1 co-purifies with the retinoblastoma (Rb) tumour suppressor gene product, E2F1, and HDAC1. DNMT1 also cooperates with Rb to repress transcription from promoters containing E2F-binding sites sμggesting a link between DNA methylation, histone deacetylase, and sequence-specific DNA binding activity, as well as a growth-regulatory pathway that is disrupted in nearly all cancer cells.