Tet1,2,3 oxidizes 5-methylcytosine to 5-hydroxymethylcytosine

Stable Identifier
R-MMU-5220944
Type
Reaction [transition]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Tet1,2,3 oxidizes 5-methylcytosine to 5-hydroxymethylcytosine
Tet1 (Tahiliani et al. 2009, Ito et al. 2010, Koh et al. 2011, Xu et al. 2011, Kaas et al. 2013, Zhang et al. 2013), Tet2 (Ito et al. 2010, Ko et al. 2010, Koh et al. 2011, Crawford et al. 2016), and Tet3 (Ito et al. 2010, Gu et al. 2011, Wossidlo et al. 2011) oxidize the 5-methyl group of 5-methylcytosine (5-mC) in DNA using molecular oxygen and 2-oxoglutarate as substrates and Fe(II) as a cofactor to yield 5-hydroxymethylcytosine (5-hmC), carbon dioxide, and succinate. Ascorbate enhances the reaction (Blaschke et al. 2013, Minor et al. 2013). Tet3 is specific to oocytes and zygotes and may be involved in demethylation of the male pronucleus after fertilization (Gu et al. 2011, Iqbal et al. 2011). Tet1 and Tet2 are expressed in embryonic stem cells and appear to be involved in differentiation (Ito et al. 2010, Koh et al. 2011).
Literature References
PubMed ID Title Journal Year
23548903 Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine

Minor, EA, Wang, G, Court, BL, Young, JI

J. Biol. Chem. 2013
23770080 Tet1 regulates adult hippocampal neurogenesis and cognition

Zhang, RR, Wu, HP, Rosa, L, Ye, P, Smith, ZD, Shi, Y, Meissner, A, Jin, S, Murai, K, Ding, YQ, Xu, ZM, Ding, C, Yang, L, Lee, YK, Tang, F, Lim, YC, Xu, GL, Liu, W, Cui, QY

Cell Stem Cell 2013
21295276 Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells

Koh, KP, Rao, A, Huang, Y, Rodig, SJ, Laiho, A, Lahesmaa, R, Cunniff, K, Orkin, SH, Sommer, CA, Yabuuchi, A, Rao, S, Nardone, J, Mostoslavsky, G, Daley, GQ, Tahiliani, M

Cell Stem Cell 2011
26734843 Tet2 Catalyzes Stepwise 5-Methylcytosine Oxidation by an Iterative and de novo Mechanism

Garcia, BA, Crawford, DJ, Kohli, RM, Liu, MY, Cao, XJ, Nabel, CS

J. Am. Chem. Soc. 2016
21892189 The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes

Pfeifer, GP, Xu, GF, Wu, HP, Yang, H, Shi, YG, Xie, ZG, He, X, Deng, Z, Szabó, PE, Gu, TP, Li, J, Jin, SG, Shi, L, Xu, GL, Guo, F, Iqbal, K, Liu, W

Nature 2011
21514197 Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells

Min, J, Xu, G, Zhang, H, Barbera, AJ, Nicholson, T, Huang, S, Kong, L, Shi, YG, Wu, F, Tan, L, Xiong, L, Chen, T, Shi, Y, Zhang, K, Deng, J, Zheng, L, Xu, Y

Mol. Cell 2011
21321204 Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine

Pfeifer, GP, Szabó, PE, Jin, SG, Iqbal, K

Proc. Natl. Acad. Sci. U.S.A. 2011
21407207 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming

Nakano, T, Reik, W, Walter, J, Zakhartchenko, V, Arand, J, Nakamura, T, Wossidlo, M, Lepikhov, K, Boiani, M, Marques, CJ

Nat Commun 2011
24050399 TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation

Ming, GL, Ross, DL, Kaas, GA, Song, H, Sweatt, JD, Eason, DE, Vachhani, RV, King, JR, Zhong, C

Neuron 2013
21057493 Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2

Koh, KP, Rao, A, Ganetzky, R, Huang, Y, Aravind, L, Ko, M, Liu, XS, Bandukwala, HS, Lamperti, ED, Pape, UJ, An, J, Agarwal, S, Tahiliani, M, Jankowska, AM, Maciejewski, JP

Nature 2010
20639862 Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification

Taranova, OV, Ito, S, D'Alessio, AC, Sowers, LC, Zhang, Y, Hong, K

Nature 2010
23812591 Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells

Goyal, P, Blaschke, K, Lorincz, MC, Rao, A, Mahapatra, S, Zepeda-Martínez, JA, Tam, A, Hirst, M, Karimi, MM, Ebata, KT, Ramalho-Santos, M, Laird, DJ

Nature 2013
Participants
Input
Output
Event Information
Go Biological Process
DNA demethylation (0080111)
Catalyst Activity

methylcytosine dioxygenase activity of Tet1,2,3 [nucleoplasm]

Physical Entity
Tet1,2,3 [nucleoplasm] (Mus musculus)
Activity
methylcytosine dioxygenase activity (GO:0070579)
This event is regulated
Positively by
Regulator
AscH- [nucleoplasm]
Orthologous Events
TET1,2,3 oxidizes 5-methylcytosine to 5-hydroxymethylcytosine (Homo sapiens)
Authored
May, B  (2013-12-29)
Reviewed
Mukherji, M  (2014-02-21)
Pfeifer, GP  (2014-01-29)
Created
May, B  (2013-12-30)
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