Valproate induces replication-independent active DNA demethylation.

摘要: In this report, we demonstrate that valproic acid (VPA), a drug has been used for decades in the treatment of epilepsy and as mood stabilizer, triggers replication-independent active demethylation DNA. Thus, can potentially reverse DNA methylation patterns erase stable imprints on non-dividing cells. Recent discoveries support role VPA regulation methylated genes; however, mechanism unclear because it is difficult to dissociate from absence during synthesis. We therefore took advantage an assay measures independently other replication activities human embryonal kidney 293 show induces histone acetylation, demethylation, expression ectopically CMV-GFP plasmid dose-dependent manner. contrast, valpromide, analogue does not induce or CMV-GFP. Furthermore, illustrate DNA-binding protein 2/DNA demethylase (MBD2/dMTase) participates reaction since antisense knockdown MBD2/dMTase attenuates VPA-induced demethylation. Taken together, our data new action enhancing intracellular activity through its effects acetylation raises possibility reversible independent by commonly prescribed drugs.