Playing TET ris with DNA modifications

Methylation of the fifth carbon of cytosine was the first epigenetic modification to be discovered in DNA . Recently, three new DNA modifications have come to light: hydroxymethylcytosine, formylcytosine, and carboxylcytosine, all generated by oxidation of methylcytosine by Ten Eleven Translocation ( TET ) enzymes. These modifications can initiate full DNA demethylation, but they are also likely to participate, like methylcytosine, in epigenetic signalling per se . A scenario is emerging in which coordinated regulation at multiple levels governs the participation of TET s in a wide range of physiological functions, sometimes via a mechanism unrelated to their enzymatic activity. Although still under construction, a sophisticated picture is rapidly forming where, according to the function to be performed, TET s ensure epigenetic marking to create specific landscapes, and whose improper build‐up can lead to diseases such as cancer and neurodegenerative disorders.