The DNMT1 inhibitor GSK-3484862 mediates global demethylation in murine embryonic stem cells

We generated WGBS datasets from mESCs treated with the novel drug GSK-3484862 attained from two different commercial sources or the conventional DNMT1 inhitibitor 5-azacytidine. To assess efficacy, datasets were generated from mESCs treated with GSK-3484862 at two concentrations and after treatment for 6 days and 14 days each. Additionally, for comparison purposes, we generated WGBS datasets from Dnmt1/3a/3b deficient mESCs which have very low levels of DNA methylation and WT mESCs treated with DMSO which retain high levels of DNA methylation. Overall design: Examination of global DNA methylation levels in Dnmt1/3a/3b deficient mESCs and WT mESCs treated with DMSO, 5-azaycytidine or GSK-3484862. GSK-3484862 treatments lasted for 6 days or 14 days at 2µM and 10µM, before collection. GSK-3484862 from two commercial suppliers - ChemieTek and MedChemExpress - were tested simultaneously. 5-azacytdine treatments were done at 100nM or 300nM for 48 hours, after which cells were allowed to recover for 46 hours before collection for sequencing.