Epigenetic alterations associated with dexamethasone sodium phosphate through DNMT and TET in RPE cells

PURPOSE: To elucidate the mechanism behind epigenetic alteration associated with dexamethasone (DEX) sodium phosphate treatment. METHODS: We performed enzyme-linked immunosorbent assay to quantify changes in global DNA methylation and hydroxymethylation, quantitative real-time PCR (qRT-PCR) of the DNA methylation- and hydroxymethylation-related gene, in vitro DNA methyltransferase (DNMT) enzymatic activity assays with purified DNMTs, and DNA hydroxymethylation pattern with super-resolution imaging. RESULTS: We identified global DNA hypomethylation and hyper-hydroxymethylation upon DEX treatment, associated with aberrant mRNA expression levels of DNMT and ten-eleven translocation (TET) proteins. Additionally, DEX exposure could directly hinder DNMT activities. CONCLUSIONS: We showed that DEX-induced epigenetic alterations are linked to aberrant DNMT and TET expression, potentially through an essential role of DNMT.