Reaction: (1) 5-methylcytosine in DNA + 2-oxoglutarate + O2 = 5-hydroxymethylcytosine in DNA + succinate + CO2
(2) 5-hydroxymethylcytosine in DNA + 2-oxoglutarate + O2 = 5-formylcytosine in DNA + succinate + CO2 + H2O
(3) 5-formylcytosine in DNA + 2-oxoglutarate + O2 = 5-carboxycytosine in DNA + succinate + CO2
Other name(s): TET1 (gene name); TET2 (gene name); TET3 (gene name)
Systematic name: 5-methylcytosine in DNA,2-oxoglutarate:oxygen oxidoreductase
Comments: The TET proteins mediate iterative oxidation of 5-methylcytosine in DNA (5mc) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are recognized by EC 3.2.2.29, thymine-DNA glycosylase (TDG), which excises them, leaving an apyrimidinic site. Coupled with the base excision repair (BER) pathway, these activities result in a cytosine demethylation pathway.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Ito, S., D'Alessio, A.C., Taranova, O.V., Hong, K., Sowers, L.C. and Zhang, Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466 (2010) 1129-1133. [PMID: 20639862]
2. Ito, S., Shen, L., Dai, Q., Wu, S.C., Collins, L.B., Swenberg, J.A., He, C. and Zhang, Y. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333 (2011) 1300-1303. [PMID: 21778364]
3. He, Y.F., Li, B.Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C.X., Zhang, K., He, C. and Xu, G.L. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333 (2011) 1303-1307. [PMID: 21817016]
4. Maiti, A. and Drohat, A.C. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites. J. Biol. Chem. 286 (2011) 35334-35338. [PMID: 21862836]
5. Zhang, L., Lu, X., Lu, J., Liang, H., Dai, Q., Xu, G.L., Luo, C., Jiang, H. and He, C. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat. Chem. Biol. 8 (2012) 328-330. [PMID: 22327402]