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Active Turnover of DNA Methylation During Cell Fate Decisions

Overview
Journal Nat Rev Genet
Specialty Genetics
Date 2020 Oct 7
PMID 33024290
Citations 81
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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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References
1.
Greenberg M, Bourchis D . The diverse roles of DNA methylation in mammalian development and disease. Nat Rev Mol Cell Biol. 2019; 20(10):590-607. DOI: 10.1038/s41580-019-0159-6. View

2.
Deaton A, Bird A . CpG islands and the regulation of transcription. Genes Dev. 2011; 25(10):1010-22. PMC: 3093116. DOI: 10.1101/gad.2037511. View

3.
Smallwood S, Lee H, Angermueller C, Krueger F, Saadeh H, Peat J . Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat Methods. 2014; 11(8):817-820. PMC: 4117646. DOI: 10.1038/nmeth.3035. View

4.
Farlik M, Sheffield N, Nuzzo A, Datlinger P, Schonegger A, Klughammer J . Single-cell DNA methylome sequencing and bioinformatic inference of epigenomic cell-state dynamics. Cell Rep. 2015; 10(8):1386-97. PMC: 4542311. DOI: 10.1016/j.celrep.2015.02.001. View

5.
Argelaguet R, Clark S, Mohammed H, Stapel L, Krueger C, Kapourani C . Multi-omics profiling of mouse gastrulation at single-cell resolution. Nature. 2019; 576(7787):487-491. PMC: 6924995. DOI: 10.1038/s41586-019-1825-8. View