Numerous mechanisms have been proposed for DNA demethylation, in which 5-methylcytosine (bold, top right) is converted to cytosine (bold, bottom right). Current evidence supports the existence of an iterative oxidation, BER-coupled pathway (orange) in embryonic stem cells. Though some evidence exists in favor of deamination-initiated, BER-coupled repair (green) and oxidation-initiated, deamination/BER-coupled (purple) pathways, important shortcomings of these routes make them more likely to serve accessory or tissue-specific roles. Enzymes which might directly removed the oxidized 5-substituent from intermediates in demethylation are possible but none have yet been clearly identified (pink).