TET Family of Dioxygenases: Crucial Roles and Underlying Mechanisms

DNA methylation plays an important role in the epigenetic regulation of mammalian gene expression. TET (ten-eleven translocation) proteins, newly discovered demethylases, have sparked great interest since their discovery. TET proteins catalyze 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in 3 consecutive Fe(II)- and 2-oxoglutarate (2-OG)-dependent oxidation reactions. TET proteins dynamically regulate global or locus-specific 5-methylcytosine and/or 5-hydroxymethylcytosine levels by facilitating active DNA demethylation. In fact, in addition to their role as methylcytosine dioxygenases, TET proteins are closely related to histone modification, interact with metabolic enzymes as well as other proteins, and cooperate in transcriptional regulation. In this review, we summarize the recent progress in this exciting field, highlighting the molecular mechanism by which TET enzymes regulate gene expression and their functions in health and disease. We also discuss the therapeutic potential of targeting TET proteins and aberrant DNA modifications.