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Publication : FoxA-dependent demethylation of DNA initiates epigenetic memory of cellular identity.

First Author  Reizel Y Year  2021
Journal  Dev Cell Volume  56
Issue  5 Pages  602-612.e4
PubMed ID  33636105 Mgi Jnum  J:303702
Mgi Id  MGI:6511193 Doi  10.1016/j.devcel.2021.02.005
Citation  Reizel Y, et al. (2021) FoxA-dependent demethylation of DNA initiates epigenetic memory of cellular identity. Dev Cell 56(5):602-612.e4
abstractText  Tissue-specific DNA methylation patterns are created by transcription factors that recruit methylation and demethylation enzymes to cis-regulatory elements. To date, it is not known whether transcription factors are needed to continuously maintain methylation profiles in development and mature tissues or whether they only establish these marks during organ development. We queried the role of the pioneer factor FoxA in generating hypomethylated DNA at liver enhancers. We discovered a set of FoxA-binding sites that undergo regional, FoxA-dependent demethylation during organ development. Conditional ablation of FoxA genes in the adult liver demonstrated that continued FoxA presence was not required to maintain the hypomethylated state, even when massive cell proliferation was induced. This study provides strong evidence for the stable, epigenetic nature of tissue-specific DNA methylation patterns directed by lineage-determining transcription factors during organ development.
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