Active turnover of DNA methylation during cell fate decisions

Nat Rev Genet. 2021 Jan;22(1):59-66. doi: 10.1038/s41576-020-00287-8. Epub 2020 Oct 6.

Abstract

DNA methylation is a key layer of epigenetic regulation. The deposition of methylation marks relies on the catalytic activity of DNA methyltransferases (DNMTs), and their active removal relies on the activity of ten-eleven translocation (TET) enzymes. Paradoxically, in important biological contexts these antagonistic factors are co-expressed and target overlapping genomic regions. The ensuing cyclic biochemistry of cytosine modifications gives rise to a continuous, out-of-thermal equilibrium transition through different methylation states. But what is the purpose of this intriguing turnover of DNA methylation? Recent evidence demonstrates that methylation turnover is enriched at gene distal regulatory elements, including enhancers, and can give rise to large-scale oscillatory dynamics. We discuss this phenomenon and propose that DNA methylation turnover might facilitate key lineage decisions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Lineage
  • Cytosine / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • DNA Methylation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dioxygenases
  • Epigenesis, Genetic*
  • Humans
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Cytosine
  • Mixed Function Oxygenases
  • TET1 protein, human
  • Dioxygenases
  • TET2 protein, human
  • DNA (Cytosine-5-)-Methyltransferases