Ten-eleven translocation family 5-methylcytosine dioxygenase (TET)

The Ten-eleven translocation (TET) family consists of three mammalian enzymes (TET1, TET2, and TET3) that play a critical role in the epigenetic regulation of the genome by promoting DNA demethylation. These enzymes are 2-oxoglutarate-dependent dioxygenases that oxidize 5-methylcytosine into 5-hydroxymethylcytosine and subsequent derivatives, which are eventually replaced by unmethylated cytosine through the base excision repair pathway. TET2 is one of the most frequently mutated genes in hematological malignancies, including myelodysplastic syndromes and acute myeloid leukemia, where loss-of-function mutations lead to DNA hypermethylation and impaired hematopoietic differentiation. Beyond oncology, TET enzymes are vital for embryonic development and neuronal plasticity. Current therapeutic interest focuses on restoring TET activity using cofactors like Vitamin C or developing small-molecule inhibitors for specific contexts where TET activity contributes to disease progression.

Other names

TET family proteinsMethylcytosine dioxygenase2-oxoglutarate-dependent dioxygenaseTen-eleven translocation methylcytosine dioxygenaseTET1TET2TET3

TET enzymes catalyze the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) using alpha-ketoglutarate and molecular oxygen as co-substrates. This process facilitates active DNA demethylation. Therapeutic strategies involve restoring activity in mutated states (e.g., via Vitamin C) or inhibiting activity in specific cancers where TET overexpression drives pathogenesis.