The DNMT family of enzymes and their known effects on hematopoiesis and DNA methylation. The DNA methyltransferases DNMT1, DNMT3A, and DNMT3B catalyze methylation of CpG dinucleotides in genomic DNA. (A) The conserved domains, function, and biological effect of each DNMT member. (B) Currently, it is understood that DNMT3A and DNMT3B are essential for the establishment of DNA cytosine methylation as they catalyze the addition of methyl groups onto the C5 position of DNA cytosine residues without regard for the methylation status of DNA. In contrast, DNMT1 appears to be essential for maintenance of DNA methylation after DNA replication as DNMT1 (1) binds PCNA and (2) has preferential enzymatic activity for hemimethylated DNA over unmethylated DNA. DNMT3L, in contrast, lacks catalytic activity but appears to physically interact with DNMT3A and stimulate its enzymatic activity. PCNA, proliferating cell nuclear antigen; PHD, plant homeodomain; PWWP, proline tryptophan tryptophan proline.