GSE77420 | Datasets2Tools

General Information

Accession	GSE77420
Title	Molecular mechanisms of global DNA demethylation to nave pluripotency in ESC
Description	Global demethylation is part of a conserved program of epigenetic reprogramming to nave pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to nave hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, Tet1-3) nor the reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transit to 2i and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in nave ESCs, which has key parallels with those operating in primordial germ cells and early embryos.
Landing Page	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77420
Repository	Gene Expression Omnibus