TET1 (CXXC domain protein) + DNA

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This model depicts TET1 firmly attached to its specific dsDNA ligand. TET1 functions as a DNA hydroxymethylase, actively participating in DNA demethylation by converting 5mC into 5mhC through a dioxygenase domain. As a Class III CXXC domain due to its hydroxymethylase function, TET1 is categorised. In addition to two zinc-finger motifs, CXXC domains contain a 3-residue motif that interacts with a specific cytosine-rich sequence. The TET1 complex stands out in that its CXXC domain binds the CpC rather than the CpG dinucleotide. TET1 is capable of binding promiscuously to both methylated and unmethylated cystines in promoter CpG islands. Dysregulation of TET1 activity has been linked to oncogenesis, as cancer cells commonly exhibit abnormal methylation profiles. TET proteins are further involved in stem cell differentiation and maintenance. Given the unique selectivity of TET1 compared to other TET proteins, investigating the binding capability of TET1 may indicate novel directions for cancer and stem cell therapies.