Induction of DNA Demethylation: Strategies and Consequences

DNA methylation is an important epigenetic modification with a plethora of effects on cells, ranging from the regulation of gene transcription to shaping chromatin structure. Notably, DNA methylation occurs thanks to the activity of DNA methyltransferases (DNMTs), which covalently add a methyl group to the cytosine in position 5' in CpG dinucleotides. Different strategies have been developed to study the effects of DNA methylation in cells, involving either DNMTs inhibition (passive DNA demethylation) or the use of Ten-eleven translocation protein (TET) family enzymes, which directly demethylate DNA (active DNA demethylation). In this manuscript, we will briefly cover the most commonly used strategies in the last two decades to achieve DNA demethylation, along with their effects on cells. We will also discuss some of the newest inducible ways to inhibit DNMTs without remarkable side effects, as well as the effect of non-coding RNAs on DNA methylation. Lastly, we will briefly examine the use of DNA methylation inhibition in biomedical research.