DNA (cytosine-5)-methyltransferase 3A (DNMT3A)

DNA (cytosine‑5)‑methyltransferase 3A (DNMT3A) is an enzyme responsible for adding new methyl groups to cytosines within CpG dinucleotides—a process known as de novo DNA methylation. This function distinguishes it from maintenance enzymes like DNMT1. By establishing new epigenetic marks during embryogenesis or cell differentiation, it plays a critical role in regulating gene expression patterns essential for development, cellular identity, genomic imprinting, X-chromosome inactivation, heterochromatin formation, and genome stability. Mutations or dysregulation of *DNMT3A* are strongly implicated in several diseases—notably acute myeloid leukemia—and germline mutations cause overgrowth syndromes with intellectual disability. As an epigenetic regulator rather than a classical receptor or signaling protein targetable by small molecules alone,*DNMT3a* remains a key focus both for understanding disease mechanisms involving aberrant epigenetics and as an indirect therapeutic target through broader hypomethylating strategies[1][2][4].

Other names

DNA methyltransferase 3 alphaDNA (cytosine-5)-methyltransferase 3 alphaDNMT3A2DNM3A_HUMANM.HsaIIIADNA cytosine methyltransferase 3A2[2][3]

Drugs like azacitidine and decitabine act as nucleoside analogs that incorporate into DNA during replication. They trap and inhibit the activity of DNA methyltransferases by forming covalent bonds with them upon attempted catalysis, leading to hypomethylation of genomic DNA.