Tet methylcytosine dioxygenase 3 (TET3)

Tet methylcytosine dioxygenase 3 (TET3) is an α-ketoglutarate dependent dioxygenase enzyme, belonging to the TET family (TET1, TET2, TET3), that plays a central role in epigenetic regulation by catalyzing the iterative oxidation of 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine, thus facilitating DNA demethylation[8][1][6][2]. TET3 is especially critical immediately after fertilization, mediating active demethylation of the paternal genome to enable embryonic development[2][8]. It is also involved in neural lineage specification and immune cell regulation through catalytic and non-catalytic (chromatin-structural) mechanisms[3][6]. Dysregulation or mutation of TET3 is implicated in a spectrum of human diseases, including cancer, neurodevelopmental disorders, and immunological dysfunctions[7][6]. While no direct inhibitors or drugs target TET3 specifically, its family-wide modulation (by metabolites or vitamin C) is of considerable research interest for therapeutic and diagnostic applications[6][8].

Other names

Methylcytosine dioxygenase TET3CXXC10KIAA0401MGC22014hCG_40738ten-eleven translocation 3BEFAHRSprobable methylcytosine dioxygenase TET3putative methylcytosine dioxygenasetet oncogene family member 3

Small molecules (e.g., 2-hydroxyglutarate) inhibit TET3 by blocking α-ketoglutarate binding, reducing its dioxygenase activity and impairing DNA demethylation[6]. Vitamin C acts as a pharmacological cofactor, enhancing TET3 catalytic activity and promoting DNA demethylation[6].