Methylation

Epigenetics of physical exercise

Biology

Gene

Epigenomics

Gene expression

DNA demethylation

DNA methylation

Epigenetics

Genetics

Methyltransferase

Nature Reviews Genetics

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. Recent studies have demonstrated that concomitant activity of de novo methylation and demethylation machineries results in rapid turnover of DNA methylation in certain contexts. The authors review this phenomenon and propose that DNA methylation turnover may facilitate key lineage decisions.

Active turnover of DNA methylation during cell fate decisions