TET1 (CXXC domain protein) + DNA

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This model is of TET1 bound to its specific dsDNA ligand. TET1 is a DNA hydroxymethylase. It plays an active role in DNA demethylation by catalysing the conversion of 5mC to 5mhC, via a dioxygenase domain. TET1 is categorised as having a Class III CXXC domain due to its hydroxymethylase function. In addition to two zinc-finger motifs, CXXC domains contain a 3-residue motif which interacts with a specific cytosine-rich sequence. The TET1 complex is unique in that its CXXC domain binds the CpC rather than the CpG dinucleotide. TET1 can bind promiscuously to both methylated and unmethylated cystines in promoter CpG islands. Dysregulation of TET1 activity has been implicated in oncogenesis, as cancer cells commonly feature abnormal methylation profiles. TET proteins are further active 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 direction for cancer and stem cell therapies.