FGF Signaling Inhibition in ESCs Drives Rapid Genome-wide Demethylation to the Epigenetic Ground State of Pluripotency

ABSTRACT: Genome-wide erasure of DNA methylation takes place in primordial germ cells (PGCs) and early embryos but the signalling mechanisms that induce reprogramming are unknown. Here we show that inhibition of Erk1/2 and Gsk3bM-BM- signalling in mouse embryonic stem cells (ESCs) by small molecule inhibitors (PD0325901 and CHIR99021, hereafter called 2i)M-BM- induces genome-wide demethylation on a scale similar to that in PGCs and early embryos, with only major satellites, intracisternal A particles (IAPs) and imprinted genes relatively resistant to erasure. Demethylation involves oxidation of 5-methylcytosine (5mC) in part by Tet1 together with repression of theM-BM- de novoM-BM- methyltransferases (Dnmt3a, Dnmt3b) and their regulator Dnmt3L and we identify aM-BM- cis-acting regulatory region inM-

ORGANISM(S): Mus musculus

SUBMITTER: Felix Krueger 

PROVIDER: E-GEOD-42923 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress