t cell transcription factor 1


Summary: A TCF transcription factor that was originally identified as a DNA-binding protein that interacts with the enhancers of T-CELL RECEPTOR ALPHA GENES. It plays a role in T-LYMPHOCYTE development.

Top Publications

  1. Xie H, Huang Z, Wang R, Sun Z. Regulation of thymocyte survival by transcriptional coactivators. Crit Rev Immunol. 2006;26:475-86 pubmed
    ..Thus, transcriptional coactivators are a substantial component of the transcriptional machinery to regulate thymocye survival, ensuring the completion of T-cell development. ..
  2. Jeannet G, Boudousquié C, Gardiol N, Kang J, Huelsken J, Held W. Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory. Proc Natl Acad Sci U S A. 2010;107:9777-82 pubmed publisher
  3. Mazumdar J, O Brien W, Johnson R, Lamanna J, Chavez J, Klein P, et al. O2 regulates stem cells through Wnt/?-catenin signalling. Nat Cell Biol. 2010;12:1007-13 pubmed publisher
    ..This decline correlates with reduced Wnt/?-catenin signalling in the subgranular zone. O2 availability, therefore, may have a direct role in stem cell regulation through HIF-1? modulation of Wnt/?-catenin signalling...
  4. Weber B, Chi A, Chavez A, Yashiro Ohtani Y, Yang Q, Shestova O, et al. A critical role for TCF-1 in T-lineage specification and differentiation. Nature. 2011;476:63-8 pubmed publisher
    ..Our data suggest a model where Notch signals induce TCF-1, and TCF-1 in turn imprints the T-cell fate by upregulating expression of T-cell essential genes. ..
  5. Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldschmeding R, et al. Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1. Science. 1999;285:1923-6 pubmed
    ..Tcf1 may act as a feedback repressor of beta-catenin-Tcf4 target genes and thus may cooperate with APC to suppress malignant transformation of epithelial cells. ..
  6. Noble J, White A, Lazzeroni L, Valdes A, Mirel D, Reynolds R, et al. A polymorphism in the TCF7 gene, C883A, is associated with type 1 diabetes. Diabetes. 2003;52:1579-82 pubmed
    ..04). These data also suggest that TCF7 C883A may affect age of disease onset. Analysis of genotype data from surrounding SNPs suggests that this TCF7 polymorphism may itself represent a risk factor for type 1 diabetes. ..
  7. Galceran J, Hsu S, Grosschedl R. Rescue of a Wnt mutation by an activated form of LEF-1: regulation of maintenance but not initiation of Brachyury expression. Proc Natl Acad Sci U S A. 2001;98:8668-73 pubmed
    ..Together, these data provide genetic evidence that Lef1 mediates the Wnt3a signal and regulates the stable maintenance of Brachyury expression during gastrulation. ..
  8. Railo A, Pajunen A, Itäranta P, Naillat F, Vuoristo J, Kilpeläinen P, et al. Genomic response to Wnt signalling is highly context-dependent--evidence from DNA microarray and chromatin immunoprecipitation screens of Wnt/TCF targets. Exp Cell Res. 2009;315:2690-704 pubmed publisher
    ..Taken together, our approaches give an insight into the complex context-dependent nature of Wnt pathway transcriptional responses and identify Disabled-2 as a potential new direct target for Wnt signalling. ..
  9. van der Flier L, Sabates Bellver J, Oving I, Haegebarth A, De Palo M, Anti M, et al. The Intestinal Wnt/TCF Signature. Gastroenterology. 2007;132:628-32 pubmed
    ..The genes were invariably expressed in adenomas, yet could be subdivided into 3 modules, based on expression in distinct crypt compartments. A module of 17 genes was specifically expressed at the position of the crypt stem cell. ..

More Information


  1. Yu Q, Sharma A, Sen J. TCF1 and beta-catenin regulate T cell development and function. Immunol Res. 2010;47:45-55 pubmed publisher
    ..We have also demonstrated a function for TCF1 and beta-catenin downstream of TCR signaling in the differentiation of mature CD4 T cells into T helper lineages. ..
  2. Willinger T, Freeman T, Herbert M, Hasegawa H, McMichael A, Callan M. Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo. J Immunol. 2006;176:1439-46 pubmed
    ..Altogether, our study suggests that proteins involved in the WNT signaling pathway not only regulate T cell development, but also peripheral T cell differentiation. ..
  3. Xie H, Huang Z, Sadim M, Sun Z. Stabilized beta-catenin extends thymocyte survival by up-regulating Bcl-xL. J Immunol. 2005;175:7981-8 pubmed
    ..beta-Catenin/TCF is thus able to act as a signal to up-regulate Bcl-xL levels in DP thymocytes, resulting in their enhanced survival. ..
  4. Yu Q, Erman B, Park J, Feigenbaum L, Singer A. IL-7 receptor signals inhibit expression of transcription factors TCF-1, LEF-1, and RORgammat: impact on thymocyte development. J Exp Med. 2004;200:797-803 pubmed
    ..We conclude that IL-7R signals down-regulate transcription factors required for the ISP to DP transition and so must be terminated by the ISP stage of thymocyte development. ..
  5. Yu Q, Sharma A, Ghosh A, Sen J. T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis. J Immunol. 2011;186:3946-52 pubmed publisher
    ..Thus, TCF1, a constitutively expressed T cell-specific transcription factor, is a critical negative regulator of the inflammatory potential of TCR-activated T cells and autoimmunity. ..
  6. Germar K, Dose M, Konstantinou T, Zhang J, Wang H, Lobry C, et al. T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling. Proc Natl Acad Sci U S A. 2011;108:20060-5 pubmed publisher
    ..Our data thus add an important functional relationship to the roadmap of T-cell development. ..
  7. van de Wetering M, Oosterwegel M, Dooijes D, Clevers H. Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box. EMBO J. 1991;10:123-32 pubmed
    ..These results identify TCF-1 as a T cell-specific transcription factor, which might play a role in the establishment of the mature T cell phenotype. ..
  8. Ioannidis V, Beermann F, Clevers H, Held W. The beta-catenin--TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival. Nat Immunol. 2001;2:691-7 pubmed
    ..Thus, TCF-1, upon association with beta-catenin, transiently ensures the survival of immature T cells, which enables them to generate and edit T cell receptor (TCR) alpha chains and attempt TCR-mediated positive selection. ..
  9. Hovanes K, Li T, Munguia J, Truong T, Milovanovic T, Lawrence Marsh J, et al. Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nat Genet. 2001;28:53-7 pubmed
  10. Galceran J, Farinas I, Depew M, Clevers H, Grosschedl R. Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice. Genes Dev. 1999;13:709-17 pubmed
    ..Together, these data provide evidence for a redundant role of LEF-1 and TCF-1 in Wnt signaling during mouse development. ..
  11. Okamura R, Sigvardsson M, Galceran J, Verbeek S, Clevers H, Grosschedl R. Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1. Immunity. 1998;8:11-20 pubmed
    ..Together, these data show that LEF-1 and TCF-1 are redundant in the regulation of T cell differentiation and gene expression. ..
  12. Wu J, Seay M, Schulz V, Hariharan M, Tuck D, Lian J, et al. Tcf7 is an important regulator of the switch of self-renewal and differentiation in a multipotential hematopoietic cell line. PLoS Genet. 2012;8:e1002565 pubmed publisher
    ..These studies in EML cells demonstrate fundamental cell-intrinsic properties of the switch between self-renewal and differentiation, and yield valuable insights for manipulating HSCs and other differentiating systems. ..
  13. Love J, Li X, Case D, Giese K, Grosschedl R, Wright P. Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature. 1995;376:791-5 pubmed
    ..The structure reveals the HMG domain bound in the widened minor groove of a markedly distorted and bent double helix. The basic region binds across the narrowed major groove and contributes to DNA recognition. ..
  14. Verbeek S, Izon D, Hofhuis F, Robanus Maandag E, te Riele H, van de Wetering M, et al. An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature. 1995;374:70-4 pubmed
    ..We conclude that Tcf-1 controls an essential step in thymocyte differentiation. ..
  15. Katoh M, Katoh M. NUMB is a break of WNT-Notch signaling cycle. Int J Mol Med. 2006;18:517-21 pubmed
  16. Oosterwegel M, van de Wetering M, Timmerman J, Kruisbeek A, Destree O, Meijlink F, et al. Differential expression of the HMG box factors TCF-1 and LEF-1 during murine embryogenesis. Development. 1993;118:439-48 pubmed
    ..Postnatally, expression of both genes could only be detected in lymphoid tissues. These observations suggest that TCF-1 and LEF-1 exert differential functions during murine embryogenesis. ..
  17. Huang Z, Xie H, Ioannidis V, Held W, Clevers H, Sadim M, et al. Transcriptional regulation of CD4 gene expression by T cell factor-1/beta-catenin pathway. J Immunol. 2006;176:4880-7 pubmed
    ..Thus, our results demonstrated that TCF/beta-catenin pathway enhances CD4 expression in vivo by recruiting TCF-1 to stimulate CD4 enhancer activity. ..
  18. van de Wetering M, Castrop J, Korinek V, Clevers H. Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties. Mol Cell Biol. 1996;16:745-52 pubmed
  19. Yu S, Zhou X, Steinke F, Liu C, Chen S, Zagorodna O, et al. The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity. 2012;37:813-26 pubmed publisher
    ..TCF-1 thus has dual roles, i.e., acting cooperatively with LEF-1 to promote thymocyte maturation while restraining LEF-1 expression to prevent malignant transformation of developing thymocytes. ..
  20. Goux D, Coudert J, Maurice D, Scarpellino L, Jeannet G, Piccolo S, et al. Cooperating pre-T-cell receptor and TCF-1-dependent signals ensure thymocyte survival. Blood. 2005;106:1726-33 pubmed
    ..The 2 pathways thus have to cooperate to ensure thymocyte survival at the pre-TCR stage. ..
  21. Hikasa H, Sokol S. Phosphorylation of TCF proteins by homeodomain-interacting protein kinase 2. J Biol Chem. 2011;286:12093-100 pubmed publisher
    ..These observations emphasize a critical role for Wnt/HIPK2-dependent TCF phosphorylation and suggest that TCF switching is an important mechanism of Wnt target gene activation in vertebrate embryos...
  22. Schilham M, Wilson A, Moerer P, Benaissa Trouw B, Cumano A, Clevers H. Critical involvement of Tcf-1 in expansion of thymocytes. J Immunol. 1998;161:3984-91 pubmed
    ..As Tcf-1 is a critical component in the Wnt/beta-catenin signaling pathway, these data suggest that Wnt-like factors play a role in the expansion of double-negative thymocytes. ..
  23. Zhou X, Xue H. Cutting edge: generation of memory precursors and functional memory CD8+ T cells depends on T cell factor-1 and lymphoid enhancer-binding factor-1. J Immunol. 2012;189:2722-6 pubmed publisher
    ..Thus, TCF-1 and LEF-1 cooperatively regulate generation of memory precursors and protective memory CD8+ T cells. ..
  24. Zhou X, Yu S, Zhao D, Harty J, Badovinac V, Xue H. Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity. 2010;33:229-40 pubmed publisher
    ..Our studies thus identify TCF-1 as a critical player in a transcriptional program that regulates memory CD8 differentiation and longevity. ..
  25. Ma J, Wang R, Fang X, Ding Y, Sun Z. Critical role of TCF-1 in repression of the IL-17 gene. PLoS ONE. 2011;6:e24768 pubmed publisher
    ..This TCF-1-mediated repression of IL-17 is critical for peripheral T cells to generate balanced immune responses. ..
  26. Erlich H, Valdes A, Julier C, Mirel D, Noble J. Evidence for association of the TCF7 locus with type I diabetes. Genes Immun. 2009;10 Suppl 1:S54-9 pubmed publisher
    ..03; transmission=52.9% in non-DR3/DR4; P=0.03). These results support the previously reported association of the non-synonymous Pro-Thr SNP in TCF7 with T1D, and suggest that other alleles at this locus may also confer risk. ..
  27. Yu Q, Sharma A, Oh S, Moon H, Hossain M, Salay T, et al. T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma. Nat Immunol. 2009;10:992-9 pubmed publisher
    ..Thus, TCF-1 initiates T(H)2 differentiation of activated CD4(+) T cells by promoting GATA-3 expression and suppressing IFN-gamma expression. ..
  28. Jatzek A, Tejera M, Singh A, Sullivan J, Plisch E, Suresh M. p27(Kip1) negatively regulates the magnitude and persistence of CD4 T cell memory. J Immunol. 2012;189:5119-28 pubmed publisher
    ..Collectively, these findings provide key insights into the mechanisms underlying the governance of peripheral CD4 T cell homeostasis and identify p27(Kip1) as a target to enhance vaccine-induced CD4 T cell memory. ..
  29. Qu L, Li J, Zhao Z, Jiang H, Zhang Q. Differential Expression of miR-202 and Validation of Predicted Target Genes in the Skin Tissue of C57BL/6 Black Mice and BALB/c White Mice. DNA Cell Biol. 2017;36:443-450 pubmed publisher
    ..Altogether, this study has shown that the expression of miR-202 was different in the skin tissue of C57BL/6 black mice and BALB/c white mice and that wnt5a, kit, and tcf7 are negatively regulated by miR-202. ..
  30. Li G, Wang Z. Retinoblastoma suppressor associated protein 46 (RbAp46) attenuates the beta-catenin/TCF signaling through up-regulation of GSK-3beta expression. Anticancer Res. 2006;26:4511-8 pubmed
    ..RbAp46 plays an important role in regulation of beta-catenin expression and the beta-catenin/TCF signaling pathway presumably through regulation of GSK-3beta expression. ..
  31. Schmidt M, Patterson M, Farrell E, Munsterberg A. Dynamic expression of Lef/Tcf family members and beta-catenin during chick gastrulation, neurulation, and early limb development. Dev Dyn. 2004;229:703-7 pubmed
  32. Gehrke I, Gandhirajan R, Kreuzer K. Targeting the WNT/beta-catenin/TCF/LEF1 axis in solid and haematological cancers: Multiplicity of therapeutic options. Eur J Cancer. 2009;45:2759-67 pubmed publisher
    ..Furthermore, we discuss the possible strategies to target this pathway and their potential importance in cancer treatment. ..
  33. Mayer K, Wolff E, Clevers H, Ballhausen W. The human high mobility group (HMG)-box transcription factor TCF-1: novel isoforms due to alternative splicing and usage of a new exon IXA. Biochim Biophys Acta. 1995;1263:169-72 pubmed
  34. Dooijes D, van Beest M, van de Wetering M, Boulanger G, Jones T, Clevers H, et al. Genomic organization of the segment polarity gene pan in Drosophila melanogaster. Mol Gen Genet. 1998;258:45-52 pubmed
    ..We present evidence suggesting that the protein encoded by pan is more similar to mammalian TCF-1 and Caenorhabditis elegans POP-1 than to mammalian LEF-1. ..
  35. Batlle E, Henderson J, Beghtel H, van den Born M, Sancho E, Huls G, et al. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell. 2002;111:251-63 pubmed
    ..We conclude that in the intestinal epithelium beta-catenin and TCF couple proliferation and differentiation to the sorting of cell populations through the EphB/ephrin-B system...
  36. Mao C, Byers S. Cell-context dependent TCF/LEF expression and function: alternative tales of repression, de-repression and activation potentials. Crit Rev Eukaryot Gene Expr. 2011;21:207-36 pubmed
    ..We also illustrate how the p53 and nuclear receptor family of transcription factors, known to control cell fate and to inhibit Wnt signaling, may participate in the fine tuning of TCF7/LEF1 repression/activation potentials. ..
  37. Ioannidis V, Kunz B, Tanamachi D, Scarpellino L, Held W. Initiation and limitation of Ly-49A NK cell receptor acquisition by T cell factor-1. J Immunol. 2003;171:769-75 pubmed
    ..We thus propose that Ly-49A receptor expression is induced from a single allele in occasional NK cells due to a limitation in the amount of a transcription factor complex requiring TCF-1. ..
  38. Maier E, Hebenstreit D, Posselt G, Hammerl P, Duschl A, Horejs Hoeck J. Inhibition of suppressive T cell factor 1 (TCF-1) isoforms in naive CD4+ T cells is mediated by IL-4/STAT6 signaling. J Biol Chem. 2011;286:919-28 pubmed publisher
    ..Thus, this study provides a model for an IL-4/STAT6-dependent fine tuning mechanism of TCF-1-driven T helper cell polarization. ..
  39. Ghogomu S, van Venrooy S, Ritthaler M, Wedlich D, Gradl D. HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor-driven transcription. J Biol Chem. 2006;281:1755-64 pubmed
  40. Shafer S, Towler D. Transcriptional regulation of SM22alpha by Wnt3a: convergence with TGFbeta(1)/Smad signaling at a novel regulatory element. J Mol Cell Cardiol. 2009;46:621-35 pubmed publisher
    ..RNAi "knockdown" of beta-catenin inhibited Wnt3a induction of SM22alpha. Thus, Wnt/beta-catenin signaling interacts with TGFbeta/Smad pathways to control SM22alpha gene transcription. ..
  41. Park M, Choi K, Jeong S. Inhibition of the DNA binding by the TCF-1 binding RNA aptamer. Biochem Biophys Res Commun. 2005;330:11-7 pubmed
    ..Similar approach may well be applicable to other proteins, especially DNA binding transcription factors, in order to modulate their DNA binding and transcriptional activity in the cells. ..
  42. Held W, Clevers H, Grosschedl R. Redundant functions of TCF-1 and LEF-1 during T and NK cell development, but unique role of TCF-1 for Ly49 NK cell receptor acquisition. Eur J Immunol. 2003;33:1393-8 pubmed
    ..The proper formation of this repertoire depends to a large extent on TCF-1. These findings suggest common and distinct functions of TCF-1 and LEF-1 during lymphocyte development. ..
  43. Kim H, van den Heuvel A, Schmidt J, Ross S. Novel common integration sites targeted by mouse mammary tumor virus insertion in mammary tumors have oncogenic activity. PLoS ONE. 2011;6:e27425 pubmed publisher
    ..As Tcf7l2, Antxr1/Tem8, and Arhgap18 have been associated with human breast and other cancers, these data demonstrate that MMTV-induced insertional mutation remains an important means for identifying genes involved in breast cancer. ..
  44. Columbus J, Chiang Y, Shao W, Zhang N, Wang D, Gaisano H, et al. Insulin treatment and high-fat diet feeding reduces the expression of three Tcf genes in rodent pancreas. J Endocrinol. 2010;207:77-86 pubmed publisher
    ..We suggest that hyperinsulinemia represses Tcf gene expression in the pancreas. Whether and how this reduction alters the function of pancreatic ? cells during hyperinsulinemia deserves further investigation. ..
  45. Klingel S, Morath I, Strietz J, Menzel K, Holstein T, Gradl D. Subfunctionalization and neofunctionalization of vertebrate Lef/Tcf transcription factors. Dev Biol. 2012;368:44-53 pubmed publisher
    ..We propose that the vertebrate specific diversification of Tcfs in vertebrates resulted in subfunctionalization of a Tcf that already united most of the Lef/Tcf functions...
  46. McQueeney K, Soufer R, Dealy C. Beta-catenin-dependent Wnt signaling in apical ectodermal ridge induction and FGF8 expression in normal and limbless mutant chick limbs. Dev Growth Differ. 2002;44:315-25 pubmed
    ..The results of this study suggest that the limbless gene is required for beta-catenin-dependent Wnt signaling in limb ectoderm leading to FGF8 expression and AER formation. ..
  47. Takahashi Yanaga F, Yoshihara T, Jingushi K, Miwa Y, Morimoto S, Hirata M, et al. Celecoxib-induced degradation of T-cell factors-1 and -4 in human colon cancer cells. Biochem Biophys Res Commun. 2008;377:1185-90 pubmed publisher
    ..Our results suggest that TCF-1 and TCF-4 degradation may involve the inhibition of the Wnt/beta-catenin signaling pathway induced by celecoxib. ..
  48. Hess Michelini R, Doedens A, Goldrath A, Hedrick S. Differentiation of CD8 memory T cells depends on Foxo1. J Exp Med. 2013;210:1189-200 pubmed publisher
    ..Collectively, these results demonstrate an intrinsic role for FOXO1 in establishing the post-effector memory program that is essential to forming long-lived memory cells capable of immune reactivation. ..
  49. Keerthivasan S, Aghajani K, Dose M, Molinero L, Khan M, Venkateswaran V, et al. ?-Catenin promotes colitis and colon cancer through imprinting of proinflammatory properties in T cells. Sci Transl Med. 2014;6:225ra28 pubmed publisher
    ..On the basis of these findings, we conclude that activation of Wnt/?-catenin signaling in effector T cells and/or Tregs is causatively linked with the imprinting of proinflammatory properties and the promotion of colon cancer. ..
  50. Katoh Y, Katoh M. Comparative integromics on Angiopoietin family members. Int J Mol Med. 2006;17:1145-9 pubmed
    ..Human ANGPTL7, characterized as potent target gene of WNT/ beta-catenin signaling pathway, is a pharmacogenomics target in the fields of oncology and regenerative medicine. ..
  51. Ro l G, van den Broek O, Spieker N, Peterson Maduro J, Destr e O. Tcf-1 expression during Xenopus development. Gene Expr Patterns. 2003;3:123-6 pubmed
    ..At tailbud stages expression is localized in specific areas of the brain, in the eyes, the otic vesicle, branchial arches and head mesenchyme, somites, tailbud, pronephros and pronephric duct...
  52. Lee H, Lee D, Park M, Yang S, Lee J, Kim D, et al. STMN2 is a novel target of beta-catenin/TCF-mediated transcription in human hepatoma cells. Biochem Biophys Res Commun. 2006;345:1059-67 pubmed
    ..Our results suggest that STMN2 might be a novel player of beta-catenin/TCF-mediated carcinogenesis in the liver. ..
  53. Tokoro Y, Sugawara T, Yaginuma H, Nakauchi H, Terhorst C, Wang B, et al. A mouse carrying genetic defect in the choice between T and B lymphocytes. J Immunol. 1998;161:4591-8 pubmed
    ..Thus, tg epsilon26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective. ..