The DNA methyltransferase family: a versatile toolkit for epigenetic regulation

Key Points The DNA methyltransferases (DNMTs) are a conserved family of cytosine methylases with a key role in epigenetic regulation. DNMT activity is highly regulated. Key regulatory mechanisms include molecular interactions, post-translational modifications, alternative splicing and gene duplication or gene loss. The molecular functions of DNMTs are not limited to gene silencing and can also include transcriptional activation and post-transcriptional regulation. The latter function is mediated by DNMT2-dependent RNA methylation. DNMTs are important for normal mammalian development, and DNMT mutations are associated with several human diseases, including cancer. The DNA methyltransferase (DNMT) family comprises a conserved set of DNA-modifying enzymes. Recent studies have increased our understanding of how DNMT activity is regulated and revealed that, in addition to establishing and maintaining DNA methylation patterns, DNMT enzymes function in transcriptional silencing, transcriptional activation and post-transcriptional regulation. The DNA methyltransferase (DNMT) family comprises a conserved set of DNA-modifying enzymes that have a central role in epigenetic gene regulation. Recent studies have shown that the functions of the canonical DNMT enzymes — DNMT1, DNMT3A and DNMT3B — go beyond their traditional roles of establishing and maintaining DNA methylation patterns. This Review analyses how molecular interactions and changes in gene copy numbers modulate the activity of DNMTs in diverse gene regulatory functions, including transcriptional silencing, transcriptional activation and post-transcriptional regulation by DNMT2-dependent tRNA methylation. This mechanistic diversity enables the DNMT family to function as a versatile toolkit for epigenetic regulation.