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An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C
Published on: June 1, 2018
Silver Nanoparticles Induce TET-Dependent Genome-Wide DNA Hydroxymethylation Alterations in Mouse Embryonic Stem
Shaokun Chen1,2, Junfa Yin1, Weiyi Lai1
1The State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China.
Abstract:
Exposure to silver nanoparticles (AgNPs) poses potential health risks. Epigenetic alterations are increasingly recognized as a critical mechanistic bridge between environmental stressors and adverse toxicological outcomes. Here, we demonstrate that exposure to noncytotoxic concentrations of AgNPs induces significant genome-wide alterations in DNA hydroxymethylation in mouse embryonic stem cells, which primarily is mediated by TET dioxygenase-dependent pathways. Further investigation shows that AgNPs activate TETs through a reactive oxygen species (ROS)-dependent manner, independent of the Ag+ ion. Our findings provide evidence that AgNPs disrupt TET-mediated DNA demethylation and reveal a novel epigenetic mechanism by which nanoparticles perturb DNA methylation homeostasis during early embryonic development.
