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.
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Acknowledgements
The authors thank members of the Reik and Rulands laboratories, in particular B. Kiani, for helpful discussions. A.P. is supported by a Sir Henry Wellcome Fellowship (215912/Z/19/Z). Research in the Reik laboratory is supported by the Biotechnology and Biological Sciences Research Council (BB/K010867/1) and the Wellcome Trust (095645/Z/11/Z).
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Parry, A., Rulands, S. & Reik, W. Active turnover of DNA methylation during cell fate decisions. Nat Rev Genet 22, 59–66 (2021). https://doi.org/10.1038/s41576-020-00287-8
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DOI: https://doi.org/10.1038/s41576-020-00287-8
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