DNA methyltransferases (DNMTs) are highly conserved enzymes that catalyze the transfer of a methyl group from S-adenosylmethionine (SAM) to cytosine residues within CpG dinucleotides, generating 5-methylcytosine (5mC). This epigenetic modification regulates gene expression, chromatin organization, genome stability, and normal development.
Major DNMT Family Members
The mammalian DNMT family comprises four principal enzymes and one regulatory cofactor with distinct biological functions:
- DNMT1: Maintains DNA methylation patterns following DNA replication.
- DNMT3A & DNMT3B: Establish de novo methylation during embryogenesis, germ cell development, and lineage specification.
- DNMT2: Primarily methylates transfer RNA (tRNA), supporting RNA stability and stress responses.
- DNMT3L: Catalytically inactive cofactor that enhances DNMT3A/3B activity during germline development.
Biological Significance
DNMTs regulate developmental epigenetic programming, transcriptional silencing, repetitive element suppression, and genome integrity. Aberrant DNMT expression or mutations contribute to cancer, developmental disorders, and age-related epigenetic alterations. Consequently, DNMT inhibitors such as azacitidine and decitabine are widely used epigenetic therapies for hematological malignancies and remain promising targets for precision medicine.
