PerspectiveEpigenetics

The push and pull of DNA methylation

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Science  09 Apr 2021:
Vol. 372, Issue 6538, pp. 128-129
DOI: 10.1126/science.abh3187

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Summary

DNA methylation is an important covalent modification of mammalian genomic DNA that represses transcription. Genomic DNA is mostly maintained with high amounts of methylation, but some regions such as CpG islands are nearly perpetually unmethylated. Recently, large valleys or canyons of unmethylated DNA were discovered throughout the mammalian genome (1, 2). Most are associated with conserved developmental regulators, such as homeobox genes, and are thought to be actively regulated. The size of these canyons is maintained by a push and pull interplay between DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) dioxygenases that oxidize 5-methylcytosine, which leads to demethylation (2). On page 146 of this issue, Dixon et al. (3) identify QSER1 (glutamine and serine–rich protein 1) as part of the “push” protection mechanism that restricts DNA methylation. They show that QSER1 cooperates with TET1 by antagonizing chromatin binding of DNMT3A and DNMT3B, thus helping to retain the developmental potential of stem cells.

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