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Cell biology

DNMT (DNA methyltransferases)

DEDNMT (DNA-Methyltransferasen)

DNA methyltransferases (DNMTs) are the enzymes that add methyl tags to your DNA. They move a methyl group from SAM (S-adenosylmethionine) onto a cytosine base, mostly at 'CpG' sites. In mammals, three active enzymes do most of the work. DNMT1, working with a partner (UHRF1), recognizes half-methylated CpGs at the DNA-copying fork and copies the methylation onto the new strand. (That is 'maintenance' methylation.) DNMT3A and DNMT3B lay down brand-new methylation during development and in adult stem cells (that is 'de novo' methylation), with a helper protein (DNMT3L) supporting it in the germline. DNA methylation shapes gene activity, X-chromosome inactivation, imprinting, and the silencing of jumping genes. With age, methylation 'drift' builds up. And somatic loss-of-function mutations in DNMT3A are a leading driver of clonal hematopoiesis, which contributes to age-related disease.

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Sources

  1. Bestor TH. (2000). The DNA methyltransferases of mammals. Human Molecular Geneticsdoi:10.1093/hmg/9.16.2395
  2. Jaiswal S, Fontanillas P, Flannick J, et al. (2014). Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. New England Journal of Medicinedoi:10.1056/NEJMoa1408617
  3. Gao L, Emperle M, Guo Y, et al. (2020). Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms. Nature Communicationsdoi:10.1038/s41467-020-17109-4