Widespread recovery of methylation at gametic imprints in hypomethylated mouse stem cells following rescue with DNMT3A2

Avinash Thakur, Sarah-Jayne Mackin, Rachelle Irwin, Karla M. O’Neill, Gareth Pollin, Colum P Walsh

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Abstract

Imprinted loci are paradigms of epigenetic regulation and are associated with a number of genetic disorders in human. A key characteristic of imprints is the presence of a gametic differentially methylated region (gDMR). Previous studies have indicated that DNA methylation lost from gDMRs could not be restored by DNMT1, or the de novo enzymes DNMT3A or 3B in stem cells, indicating that imprinted regions must instead undergo passage through the germline for reprogramming. However, previous studies were non-quantitative, were unclear on the requirement for DNMT3A/B and showed some inconsistencies. In addition, new putative gDMR has recently been described, along with an improved delineation of the existing gDMR locations. We therefore aimed to re-examine the dependence of methylation at gDMRs on the activities of the methyltransferases in mouse embryonic stem cells (ESCs).
Original languageEnglish
Pages (from-to)1-15
JournalEpigenetics and Chromatin
Volume9
Issue number1
DOIs
Publication statusPublished - 22 Nov 2016

Keywords

  • Imprinting
  • DNA methylation
  • Reprogramming
  • ESC

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