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Updated: Dec 6, 2025
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Published on: September 7, 2017
Active turnover of DNA methylation during cell fate decisions
Aled Parry1, Steffen Rulands2,3, Wolf Reik4
1Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK. aled.parry@babraham.ac.uk.
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.
Insights
DNA methylation turnover, involving DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, may drive cell lineage decisions. This epigenetic process creates dynamic methylation changes at regulatory elements.
Area of Science:
- Epigenetics and Molecular Biology
- Genomics and Gene Regulation
Background:
- DNA methylation is a crucial epigenetic mechanism.
- DNA methyltransferases (DNMTs) add methylation marks, while ten-eleven translocation (TET) enzymes remove them.
- Paradoxically, DNMTs and TET enzymes are often co-expressed, targeting similar genomic areas.
Purpose of the Study:
- To explore the functional significance of DNA methylation turnover.
- To investigate the role of cyclic DNA methylation dynamics in biological processes.
Main Methods:
- Review of recent evidence on DNA methylation dynamics.
- Analysis of methylation turnover at gene distal regulatory elements, including enhancers.
- Discussion of oscillatory dynamics in DNA methylation states.
Main Results:
- DNA methylation turnover is frequently observed at gene distal regulatory elements.
- This turnover can lead to large-scale oscillatory dynamics in DNA methylation.
- The phenomenon is linked to cyclic biochemistry of cytosine modifications.
Conclusions:
- DNA methylation turnover is a significant epigenetic phenomenon.
- This dynamic process may play a critical role in facilitating key cell lineage decisions.
- Understanding methylation turnover provides insights into epigenetic regulation and cell fate determination.
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