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. 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.