Oxidative DNA demethylation mediated by Tet enzymes

DNA modification, methylation of cytosine (5mC), and oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) can have profound effects on genome function in animals. These modifications are intricately involved in DNA methylation reprograming dynamics during mammalian development. Together, they contribute to cell lineage restriction and maintenance, while also undergoing dynamic changes during cellular transitions and induced reprograming. The last five years have seen an intense research focus on enzymatic DNA demethylation, triggered by the discovery of 5hmC and Tet dioxygenases. In this review, we evaluate recent findings that have provided new insights into the mechanisms underlying DNA demethylation and its effect on developmental regulation.