Global DNA demethylation occurs in vivo in the early embryo and primordial germ cells, and in vitro during the transition of primed embryonic stem cells (ESC) to nave pluripotency. Whether such global reprogramming also occurs in the derivation of induced pluripotent stem cells (iPSC) is not known. We show that iPSC reprogramming involves two modes of DNA demethylation  global and targeted. Cells at intermediate stages of reprogramming undergo genome-wide demethylation. In parallel, regulatory regions including ESC enhancers and super-enhancers are specifically targeted for further demethylation. These regulatory regions remain demethylated at late stages of reprogramming, while the bulk of the genome undergoes remethylation. AID is essential for transient genome-wide demethylation, but not for the targeted demethylation at regulatory regions. Global and targeted DNA demethylation seem to be conserved aspects of distinct reprogramming processes, presumably because of their respective roles in epigenetic memory erasure and in the establishment of cell identity. SOURCE: Felix Krueger (felix.krueger@babraham.ac.uk) -  The Babraham Institute

Pluto Bioinformatics

GSE69823: Global and Targeted DNA Demethylation during iPSC Reprogramming