Gene Symbol: Tet3
Description: tet methylcytosine dioxygenase 3
Alias: B430006D22Rik, BC037432, D230004J03Rik, methylcytosine dioxygenase TET3, Tet methylcytosine deoxygenase 3 isoform, tet oncogene family member 3
Species: mouse
Products:     Tet3

Top Publications

  1. Tahiliani M, Koh K, Shen Y, Pastor W, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324:930-5 pubmed publisher
    ..hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC. ..
  2. Iqbal K, Jin S, Pfeifer G, SZABO P. Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc Natl Acad Sci U S A. 2011;108:3642-7 pubmed publisher
    ..It is likely that 5mC oxidation is carried out by the Tet3 oxidase...
  3. Gu T, Guo F, Yang H, Wu H, Xu G, Liu W, et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature. 2011;477:606-10 pubmed publisher
    ..Furthermore, we demonstrate that the dioxygenase Tet3 (ref. 5) is enriched specifically in the male pronucleus...
  4. Deplus R, Delatte B, Schwinn M, Defrance M, Méndez J, Murphy N, et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 2013;32:645-55 pubmed publisher
    ..linked TET1 function to epigenetic repression complexes, yet mechanistic information, especially for the TET2 and TET3 proteins, remains limited. Here, we show a direct interaction of TET2 and TET3 with O-GlcNAc transferase (OGT)...
  5. Xu Y, Xu C, Kato A, Tempel W, Abreu J, Bian C, et al. Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development. Cell. 2012;151:1200-13 pubmed publisher
    ..Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes...
  6. Ito S, D Alessio A, Taranova O, Hong K, Sowers L, Zhang Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010;466:1129-33 pubmed publisher
    ..Here we extend this study by demonstrating that all three mouse Tet proteins (Tet1, Tet2 and Tet3) can also catalyse a similar reaction...
  7. Ito S, Shen L, Dai Q, Wu S, Collins L, Swenberg J, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333:1300-3 pubmed publisher
    ..Thus, we identify two previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins. Our study raises the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation. ..
  8. Tan L, Shi Y. Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development. 2012;139:1895-902 pubmed publisher
    ..In this Primer we provide an overview of the role of Tet family proteins and 5hmC in development and cancer. ..
  9. Yamaguchi S, Hong K, Liu R, Shen L, Inoue A, Diep D, et al. Tet1 controls meiosis by regulating meiotic gene expression. Nature. 2012;492:443-7 pubmed publisher
    ..Our study thus establishes a function for Tet1 in meiosis and meiotic gene activation in female germ cells. ..

More Information


  1. Wossidlo M, Nakamura T, Lepikhov K, Marques C, Zakhartchenko V, Boiani M, et al. 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming. Nat Commun. 2011;2:241 pubmed publisher
    ..A knockdown of the 5hmC generating dioxygenase Tet3 simultaneously affects the patterns of 5hmC and 5mC in the paternal pronucleus...
  2. Lio C, Zhang J, González Avalos E, Hogan P, Chang X, Rao A. Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility. elife. 2016;5: pubmed publisher
    ..Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 ..
  3. Orlanski S, Labi V, Reizel Y, Spiro A, Lichtenstein M, Levin Klein R, et al. Tissue-specific DNA demethylation is required for proper B-cell differentiation and function. Proc Natl Acad Sci U S A. 2016;113:5018-23 pubmed publisher
    ..We show that a Tet2/Tet3 conditional knockout at early stages of B-cell development largely prevents lineage-specific programmed ..
  4. Perera A, Eisen D, Wagner M, Laube S, Künzel A, Koch S, et al. TET3 is recruited by REST for context-specific hydroxymethylation and induction of gene expression. Cell Rep. 2015;11:283-94 pubmed publisher
    ..In particular, it is not known how the neuronal TET3 isoform lacking a DNA-binding domain is targeted to the DNA...
  5. Wang H, Yang H, Shivalila C, Dawlaty M, Cheng A, Zhang F, et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell. 2013;153:910-8 pubmed publisher
    ..Thus, the CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple genes, an approach that will greatly accelerate the in vivo study of functionally redundant genes and of epistatic gene interactions. ..
  6. Dzitoyeva S, Chen H, Manev H. Effect of aging on 5-hydroxymethylcytosine in brain mitochondria. Neurobiol Aging. 2012;33:2881-91 pubmed publisher
    ..synthesis (mitochondrial DNA methyltransferase 1 [mtDNMT1] and ten-eleven-translocation [TET]1-TET3, respectively)...
  7. Yue X, Trifari S, Aijö T, Tsagaratou A, Pastor W, Zepeda Martínez J, et al. Control of Foxp3 stability through modulation of TET activity. J Exp Med. 2016;213:377-97 pubmed publisher
    ..to CNS2-deficient T reg cells, the stability of Foxp3 expression is markedly compromised in T reg cells from Tet2/Tet3 double-deficient mice...
  8. Someya K, Nakatsukasa H, Ito M, Kondo T, Tateda K, Akanuma T, et al. Improvement of Foxp3 stability through CNS2 demethylation by TET enzyme induction and activation. Int Immunol. 2017;29:365-375 pubmed publisher
    ..culture conditions, which facilitated CNS2 DNA demethylation and stabilization of Foxp3 expression in a TET2- and TET3-dependent manner...
  9. Tampe B, Tampe D, Müller C, Sugimoto H, LeBleu V, Xu X, et al. Tet3-mediated hydroxymethylation of epigenetically silenced genes contributes to bone morphogenic protein 7-induced reversal of kidney fibrosis. J Am Soc Nephrol. 2014;25:905-12 pubmed publisher
    ..Furthermore, this reversal of pathologic hypermethylation was achieved specifically through Tet3-mediated hydroxymethylation...
  10. Amouroux R, Nashun B, Shirane K, Nakagawa S, Hill P, D Souza Z, et al. De novo DNA methylation drives 5hmC accumulation in mouse zygotes. Nat Cell Biol. 2016;18:225-233 pubmed publisher
    ..reprogramming entails genome-wide DNA demethylation that is accompanied by Tet methylcytosine dioxygenase 3 (Tet3)-driven oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC; refs 1-4)...
  11. Jiang D, Wei S, Chen F, Zhang Y, Li J. TET3-mediated DNA oxidation promotes ATR-dependent DNA damage response. EMBO Rep. 2017;18:781-796 pubmed publisher
    ..ATR-dependent DDR leads to dynamic changes in 5hmC levels and TET3 enzymatic activity...
  12. Kim H, Jang W, Kang M, Jeong J, Choi M, Sung Y, et al. TET1 contributes to neurogenesis onset time during fetal brain development in mice. Biochem Biophys Res Commun. 2016;471:437-43 pubmed publisher
    ..In conclusion, TET1 makes the start time of neurogenesis earlier in the TG brains compared to that in the WT brains during fetal brain development. ..
  13. Nakamura T, Liu Y, Nakashima H, Umehara H, Inoue K, Matoba S, et al. PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos. Nature. 2012;486:415-9 pubmed publisher
    ..Here we show that PGC7 protects 5mC from Tet3-mediated conversion to 5hmC by binding to maternal chromatin containing dimethylated histone H3 lysine 9 (H3K9me2) ..
  14. Kang J, Lienhard M, Pastor W, Chawla A, Novotny M, Tsagaratou A, et al. Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis. Proc Natl Acad Sci U S A. 2015;112:E4236-45 pubmed publisher
    ..Embryos lacking Tet1 and Tet3 (Tet1/3 DKO) displayed a strong loss of 5-hydroxymethylcytosine (5hmC) and a concurrent increase in 5-..
  15. Colquitt B, Allen W, Barnea G, Lomvardas S. Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity. Proc Natl Acad Sci U S A. 2013;110:14682-7 pubmed publisher
    ..Overexpression of Tet3 in mOSNs markedly alters gene-body 5hmC levels and gene expression in a manner consistent with a positive role for ..
  16. Nakagawa T, Lv L, Nakagawa M, Yu Y, Yu C, D Alessio A, et al. CRL4(VprBP) E3 ligase promotes monoubiquitylation and chromatin binding of TET dioxygenases. Mol Cell. 2015;57:247-260 pubmed publisher
    ..Cumulatively, our data demonstrate that CRL4(VprBP) is a critical regulator of TET dioxygenases during development and in tumor suppression. ..
  17. Zhao J, Ma X, Ma J, Sun L, Lu B, Wang Y, et al. TET3 Mediates Alterations in the Epigenetic Marker 5hmC and Akt pathway in Steroid-Associated Osteonecrosis. J Bone Miner Res. 2017;32:319-332 pubmed publisher
    ..Here, we report that TET3-5hmC was upregulated in the femoral head tissues of SAON patients and MLO-Y4 cells with dexamethasone (Dex) ..
  18. Minor E, Court B, Young J, Wang G. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J Biol Chem. 2013;288:13669-74 pubmed publisher
    ..Further, blocking ascorbate entry into cells by phloretin and knocking down Tet (Tet1, Tet2, and Tet3) expression by short interference RNAs (siRNA) significantly inhibit the effect of ascorbate on 5-hmC...
  19. Tsukada Y, Akiyama T, Nakayama K. Maternal TET3 is dispensable for embryonic development but is required for neonatal growth. Sci Rep. 2015;5:15876 pubmed publisher
    ..b>TET3-mediated sequential oxidation of 5mC has recently been shown to contribute to the genome-wide loss of 5mC in the ..
  20. Yu H, Su Y, Shin J, Zhong C, Guo J, Weng Y, et al. Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair. Nat Neurosci. 2015;18:836-43 pubmed publisher
    ..We found that synaptic activity bi-directionally regulates neuronal Tet3 expression...
  21. Khoueiry R, Sohni A, Thienpont B, Luo X, Velde J, Bartoccetti M, et al. Lineage-specific functions of TET1 in the postimplantation mouse embryo. Nat Genet. 2017;49:1061-1072 pubmed publisher
    ..non-redundant roles for TET1 at an early postimplantation stage of the mouse embryo, when its paralogs Tet2 and Tet3 are not detectably expressed...
  22. Arioka Y, Watanabe A, Saito K, Yamada Y. Activation-induced cytidine deaminase alters the subcellular localization of Tet family proteins. PLoS ONE. 2012;7:e45031 pubmed publisher
    ..overexpressed Aid is mainly localized in the cytoplasm, whereas Tet1 and Tet2 are localized in the nucleus, and Tet3 is localized in both the cytoplasm and the nucleus...
  23. Chen H, Kazemier H, de Groote M, Ruiters M, Xu G, Rots M. Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter. Nucleic Acids Res. 2014;42:1563-74 pubmed publisher
    ..of targeted CpG sites in both promoters for targeted TET2 and to a lesser extent for TET1, but not for TET3. Interestingly, we observed re-activation of transcription of ICAM-1...
  24. Chamessian A, Qadri Y, Cummins M, Hendrickson M, Berta T, Buchheit T, et al. 5-Hydroxymethylcytosine (5hmC) and Ten-eleven translocation 1-3 (TET1-3) proteins in the dorsal root ganglia of mouse: Expression and dynamic regulation in neuropathic pain. Somatosens Mot Res. 2017;34:72-79 pubmed publisher
    ..the 5hmC-generating Ten-eleven translocation 1-3 (TET1-3) proteins are expressed in a cell-type specific manner in the DRG, with Tet3 displaying differential upregulation after injury, suggesting a potential role in neuropathic pain.
  25. Keil K, Altmann H, Mehta V, Abler L, Elton E, Vezina C. Catalog of mRNA expression patterns for DNA methylating and demethylating genes in developing mouse lower urinary tract. Gene Expr Patterns. 2013;13:413-24 pubmed publisher
    ..Future investigation into how DNA methylation patterns are established, maintained and remodeled during the course of embryonic prostatic bud formation may provide insight into prostate morphogenesis and disease. ..
  26. Dai H, Wang B, Yang L, Chen J, Zhu G, Sun M, et al. TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling. Nature. 2016;538:528-532 pubmed publisher
    ..These findings reveal a fundamental epigenetic mechanism featuring dynamic DNA methylation and demethylation crucial to regulation of key signalling pathways in early body plan formation. ..
  27. Tsagaratou A, González Avalos E, Rautio S, Scott Browne J, Togher S, Pastor W, et al. TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells. Nat Immunol. 2017;18:45-53 pubmed publisher
    ..We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and ..
  28. Yang J, Guo R, Wang H, Ye X, Zhou Z, Dan J, et al. Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs. Cell Rep. 2016;15:1809-21 pubmed publisher
    ..Together, Tet enzymes play important roles in telomere maintenance and chromosomal stability of ESCs by modulating sub-telomeric methylation levels. ..
  29. Zhang J, Chen S, Zhang D, Shi Z, Li H, Zhao T, et al. Tet3-Mediated DNA Demethylation Contributes to the Direct Conversion of Fibroblast to Functional Neuron. Cell Rep. 2016;17:2326-2339 pubmed publisher
    ..Here, we show that Tet3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons...
  30. Lv X, Jiang H, Liu Y, Lei X, Jiao J. MicroRNA-15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development. EMBO Rep. 2014;15:1305-14 pubmed publisher
    ..We also show that miR-15b binds to the 3' UTR of TET3, which plays crucial roles during embryonic development by enhancing DNA demethylation...
  31. Li X, Wei W, Zhao Q, Widagdo J, Baker Andresen D, Flavell C, et al. Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proc Natl Acad Sci U S A. 2014;111:7120-5 pubmed publisher
    ..Moreover, extinction learning-induced Tet3-mediated accumulation of 5-hmC is associated with the establishment of epigenetic states that promote gene ..
  32. Zhu X, Girardo D, Govek E, John K, Mellén M, Tamayo P, et al. Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation. Neuron. 2016;89:100-12 pubmed publisher
    ..Knockdown of Tet1 and Tet3 by RNAi in ex vivo cerebellar slice cultures inhibits dendritic arborization of developing GCs, a critical step ..
  33. Li X, Yue X, Pastor W, Lin L, Georges R, Chavez L, et al. Tet proteins influence the balance between neuroectodermal and mesodermal fate choice by inhibiting Wnt signaling. Proc Natl Acad Sci U S A. 2016;113:E8267-E8276 pubmed publisher
    ..Here, we show that mouse embryonic stem cells (mESCs), either lacking Tet3 alone or with triple deficiency of Tet1/2/3, displayed impaired adoption of neural cell fate and concomitantly ..
  34. Liu N, Wang M, Deng W, Schmidt C, Qin W, Leonhardt H, et al. Intrinsic and extrinsic connections of Tet3 dioxygenase with CXXC zinc finger modules. PLoS ONE. 2013;8:e62755 pubmed publisher
    ..Interestingly, in human and mouse the Tet2 and Tet3 genes are adjacent to Cxxc4 and Cxxc10-1, respectively...
  35. Peat J, Dean W, Clark S, Krueger F, Smallwood S, Ficz G, et al. Genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of TET3 oxidation. Cell Rep. 2014;9:1990-2000 pubmed publisher
    ..This involves oxidation by TET3, but our understanding of its targets and the wider context of demethylation is limited to a small fraction of the ..
  36. Ito R, Katsura S, Shimada H, Tsuchiya H, Hada M, Okumura T, et al. TET3-OGT interaction increases the stability and the presence of OGT in chromatin. Genes Cells. 2014;19:52-65 pubmed publisher
    ..Herein, we focused on TET3, the regulation of which is still unclear...
  37. An J, González Avalos E, Chawla A, Jeong M, López Moyado I, Li W, et al. Acute loss of TET function results in aggressive myeloid cancer in mice. Nat Commun. 2015;6:10071 pubmed publisher
    ..We also observe progressive accumulation of phospho-H2AX and strong impairment of DNA damage repair pathways, suggesting a key role for TET proteins in maintaining genome integrity. ..
  38. Li T, Yang D, Li J, Tang Y, Yang J, Le W. Critical role of Tet3 in neural progenitor cell maintenance and terminal differentiation. Mol Neurobiol. 2015;51:142-54 pubmed publisher
    5-Hydroxymethylcytosine (5hmC), converted from 5-methylcytocine (5mC) by Tet family of dioxygenases (Tet1, Tet2, and Tet3), is enriched in the embryonic stem cells (ESCs) and in the brain...
  39. Shin S, Vogt E, Jimenez Movilla M, Baibakov B, Dean J. Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice. Nat Commun. 2017;8:1643 pubmed publisher
    ..present in the nucleus and cytoplasm of zygotes and has been associated with protecting the female pronucleus from TET3-mediated demethylation...
  40. Fong K, Hufnagel R, Khadka V, Corley M, Maunakea A, Fogelgren B, et al. A mutation in the tuft mouse disrupts TET1 activity and alters the expression of genes that are crucial for neural tube closure. Dis Model Mech. 2016;9:585-96 pubmed publisher
    ..These results indicate that TET1 is an epigenetic determinant for regulating genes that are crucial to closure of the anterior neural tube and its mutation has implications to craniofacial development, as presented by the tuft mouse. ..
  41. Qian Y, Tu J, Tang N, Kong G, Chung J, Chan W, et al. Dynamic changes of DNA epigenetic marks in mouse oocytes during natural and accelerated aging. Int J Biochem Cell Biol. 2015;67:121-7 pubmed publisher
    ..show all the DNA demethylation marks are dynamically regulated in both aging conditions, which are associated with Tet3 over-expression and Tdg repression...
  42. Shen L, Inoue A, He J, Liu Y, Lu F, Zhang Y. Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes. Cell Stem Cell. 2014;15:459-471 pubmed publisher
    ..Recent studies have suggested that Tet3-mediated oxidation of 5-methylcytosine (5mC) and DNA replication-dependent dilution both contribute to global ..
  43. Xiao P, Zhou X, Zhang H, Xiong K, Teng Y, Huang X, et al. Characterization of the nuclear localization signal of the mouse TET3 protein. Biochem Biophys Res Commun. 2013;439:373-7 pubmed publisher
    ..The TET3 protein is a 1668-amino-acid DNA demethylase that is predicted to possess five nuclear localization signals (NLSs)...
  44. Xue S, Liu C, Sun X, Li W, Zhang C, Zhou X, et al. TET3 Inhibits Type I IFN Production Independent of DNA Demethylation. Cell Rep. 2016;16:1096-1105 pubmed publisher
    ..Here, we find that the DNA demethylase TET3 is a negative regulator of IFN-? in response to poly(I:C) stimulation or viral infection...
  45. Jin S, Zhang Z, Dunwell T, Harter M, Wu X, Johnson J, et al. Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration. Cell Rep. 2016;14:493-505 pubmed publisher
    We report that the mammalian 5-methylcytosine (5mC) oxidase Tet3 exists as three major isoforms and characterized the full-length isoform containing an N-terminal CXXC domain (Tet3FL)...
  46. Bose R, Spulber S, Kilian P, Heldring N, Lönnerberg P, Johnsson A, et al. Tet3 mediates stable glucocorticoid-induced alterations in DNA methylation and Dnmt3a/Dkk1 expression in neural progenitors. Cell Death Dis. 2015;6:e1793 pubmed publisher
    ..These alterations were dependent on Tet3 upregulation...
  47. Hatanaka Y, Tsusaka T, Shimizu N, Morita K, Suzuki T, Machida S, et al. Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes. Cell Rep. 2017;20:2756-2765 pubmed publisher
    ..Mettl23 interacts with Tet3, a 5mC-oxidizing enzyme responsible for active DNA demethylation, by binding to another maternal factor, GSE (gonad-..
  48. Zhenwei J, Shuxin G, Yongchun Z, Xianhua Z. Mechanisms of TET protein-mediated DNA demethylation and its role in the regulation of mouse development. Yi Chuan. 2015;37:34-40 pubmed publisher
    TET (ten-eleven translocation) protein family includes three members TET1, TET2 and TET3, which belong to alpha-ketoglutaric acid ( α-KG )- and Fe(2+)-dependent dioxygenase superfamily, and have the capacity to convert 5-methylcytosine ..