Year: 2017
Type: article
Abstract: Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs) is not known. Here, we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires activation-induced cytidine deaminase (AID)-mediated downregulation of UHRF1 protein, and abolishing demethylation leaves thousands of hypermethylated regions in the iPSC genome. Independently of AID and global demethylation, regulatory regions, particularly ESC enhancers and super-enhancers, are specifically targeted for hypomethylation in association with transcription of the pluripotency network. Our results show that global and targeted DNA demethylation are conserved and distinct reprogramming processes, presumably because of their respective roles in epigenetic memory erasure and in the establishment of cell identity.
Source: Cell Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: G2112608321, Wellcome Trust MRC Cambridge Stem Cell Institute, The Chemical Biology of the Genome and the Epigenome., Adaptation of a high resolution, high throughput assay of immunoglobulin repertoires for commercial and clinical applications, G5410182794, Epigenetic reprogramming in mammalian development, G5990445532, Developmental dynamics of the epigenome, Epigenetic reprogramming in mammalian development.
OpenAlex ID: W2584479592