Tet proteins contain several conserved domains (Tahiliani et al. 2009), including a CXXC domain that has high affinity for clustered unmethylated CpG dinucleotides and a catalytic domain that is typical of Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenases (Loenarz and Schofield 2011) ), mutation of iron-binding sites of Tet proteins abolishes their enzymatic activities (Tahiliani et al. 2009; Ito et al. 2010). In addition, 2-hydroxyglutarate (2-HG), a competitive inhibitor of 2OG-dependent dioxygenases, suppresses the catalytic activity of Tet proteins (W Xu et al. 2011).Both fully methylated and hemimethylated DNA in a CG or non-CG context can serve as substrates for TET1 (Tahiliani et al. 2009; Ficz et al. 2011; Pastor et al. 2011). In tumor cells, the normal pattern of DNA methylation is often altered, resulting in global hypomethylation of the genome in conjunction with hypermethylation at CpG islands within the promoters of critical genes such as tumor suppressors (Esteller, 2008).