DNMT (DNA methyltransferases)

DNA methyltransferases (DNMTs) catalyse the transfer of a methyl group from S-adenosylmethionine to the 5-carbon of cytosine, primarily at CpG dinucleotides. In mammals, three catalytically active enzymes dominate. DNMT1, in cooperation with UHRF1, recognises hemi-methylated CpGs at the replication fork and copies parental methylation onto the nascent strand, providing maintenance methylation. DNMT3A and DNMT3B establish new methylation patterns during development and in adult stem cells (de novo methylation), with the accessory protein DNMT3L supporting activity in the germline. DNA methylation patterns shape gene expression, X-chromosome inactivation, imprinting and silencing of transposable elements. With ageing, methylation drift accumulates, and somatic DNMT3A loss-of-function mutations are a leading driver of clonal haematopoiesis, contributing to age-related disease.