Methylcytosine dioxygenase TET2 (TET2)

Methylcytosine dioxygenase TET2 is a pivotal epigenetic enzyme that catalyzes the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), initiating the active DNA demethylation pathway (UniProt Q6N021). As a member of the ten-eleven translocation (TET) family of Fe(II) and 2-oxoglutarate-dependent dioxygenases, it plays a fundamental role in regulating gene expression and maintaining hematopoietic stem cell homeostasis (PubMed: 21454919). Mutations in TET2 are among the most frequent genetic alterations in myeloid malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), where they lead to DNA hypermethylation and impaired cellular differentiation (NIH: PMC5555536). Beyond oncology, TET2 deficiency is a primary driver of clonal hematopoiesis of indeterminate potential (CHIP), which is linked to an increased risk of atherosclerotic cardiovascular disease due to heightened inflammatory responses in myeloid cells (PubMed: 28106064). Therapeutic strategies focus on restoring TET2 activity using cofactors like Vitamin C, utilizing hypomethylating agents to counteract epigenetic dysregulation, or exploring synthetic lethality with PARP inhibitors (PubMed: 28823558).

Other names

Ten-eleven translocation 2Tet methylcytosine dioxygenase 2KIAA1546IMD75

TET2 catalyzes the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, facilitating DNA demethylation; therapeutic approaches involve restoring this enzymatic activity with cofactors like Vitamin C or using hypomethylating agents to bypass the deficiency.