DNMTs

DNMTs, or DNA methyltransferases, are enzymes that add a methyl group to cytosine bases in DNA, producing 5-methylcytosine. This epigenetic modification influences gene expression and genome stability and is essential for development, genomic imprinting, X-chromosome inactivation, and suppression of transposable elements.

In humans, the main DNA methyltransferases are DNMT1, DNMT3A, and DNMT3B; DNMT3L is a regulatory factor that lacks catalytic activity but supports DNMT3A/3B function. A related enzyme, DNMT2 (also called TRDMT1), methylates tRNA rather than DNA.

DNMT1 functions primarily as a maintenance methyltransferase, restoring methylation on the new strand after DNA replication, often targeted to hemi-methylated CpG sites. DNMT3A and DNMT3B establish methylation during development on unmethylated DNA (de novo methylation). DNMT3L enhances the activity of DNMT3A/3B but does not catalyze methyl transfer itself.

DNMTs use S-adenosyl-L-methionine as the methyl donor. DNMT1 and DNMT3A/3B contain regulatory domains that influence activity and chromatin targeting; DNMT3A/3B have PWWP and ADD domains that help direct them to chromatin.

Aberrant DNMT activity or misregulation is associated with cancer and other diseases. In medicine, DNMT inhibitors such as 5-azacytidine and decitabine are used to treat certain myeloid malignancies by promoting DNA hypomethylation and re-expression of silenced genes.