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

ABSTRACT:

Background

DNA methylation plays an important role in regulating gene expression in mammals. The covalent DNMT1 inhibitors 5-azacytidine and decitabine are widely used in research to reduce DNA methylation levels, but they impart severe cytotoxicity which limits their demethylation capability and confounds interpretation of experiments. Recently, a non-covalent inhibitor of DNMT1 called GSK-3484862 was developed by GlaxoSmithKline. We sought to determine whether GSK-3484862 can induce demethylation more effectively than 5-azanucleosides. Murine embryonic stem cells (mESCs) are an ideal cell type in which to conduct such experiments, as they have a high degree of DNA methylation but tolerate dramatic methylation loss.

Results

We determined the cytotoxicity and optimal concent

SUBMITTER: Azevedo Portilho N 

PROVIDER: S-EPMC8672470 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature