DNMT1 Gene

The DNMT1 gene (acronym for DNA methyltransferase 1) belongs to a family of DNA methyltransferases (DNMTs) that comprises a conserved group of DNA-modifying enzymes that plays a central role in epigenetic gene regulation.

The DNMT1 gene is a protein-coding gene located on chromosome 19p13.2. The gene encodes a protein arginine methyltransferase that catalyzes the transfer of methyl groups from S-adenosylmethionine (SAM) to the arginine residues of histones and other proteins. The enzyme is important for the maintenance of methylation patterns after DNA replication (Lyko F2018).

The DNA methyltransferase (DNMT) family comprises a conserved group of DNA-modifying enzymes that play a central role in epigenetic gene regulation. Molecular interactions and changes in gene copy number modulate the activity of DNMTs in various gene regulatory functions, such as transcriptional silencing, transcriptional activation, and post-transcriptional regulation through DNMT2-dependent tRNA methylation. The diversity of functions allows the DNMT family to function as a versatile toolbox for epigenetic regulation.

Aberrant methylation patterns are found in human tumors and are associated with developmental abnormalities. Thus, DNMTs are overexpressed in cancer cells, which may partly explain the phenomenon of hypermethylation frequently observed in tumors (Veeck J et al. 2010).

DNMT1-mediated hypermethylation of the FOXO3a promoter leads to downregulation of FOXO3a expression in breast cancer. FOXO3a is functionally related to the inhibition of FOXM1/SOX2 signaling and the resulting suppression of the properties and tumorigenicity of BCSCs. SOX2 directly transcends DNMT1 expression, thereby altering the methylation process, which in turn feedback inhibits FOXO3a expression. Inhibition of DNMT activity suppressed tumor growth by regulating FOXO3a/FOXM1/SOX2 signaling in breast cancer (Liu H et al. 2020).

Diseases associated with DNMT1 include autosomal dominant cerebellar ataxia with hearing loss and narcolepsy (G11.2; OMIM: 604121)

1. Liu H et al (2020) Downregulation of FOXO3a by DNMT1 promotes breast cancer stem cell properties and tumorigenesis. Cell Death Differ 27:966-983.
2. Lyko F(2018) The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev Genet19: 81-92.
3. Veeck J et al (2010) Breast cancer epigenetics: from DNA methylation to microRNAs. J Mammary Gland Biol Neoplasia 15:5-17.