Tcf3

Summary

Gene Symbol: Tcf3
Description: transcription factor 3
Alias: AA408400, ALF2, AW209082, E12, E12/E47, E2A, E47, KA1, ME2, Pan1, Pan2, TCF-3, Tcfe2a, VDIR, bHLHb21, transcription factor E2-alpha, immunoglobulin enhancer-binding factor E12/E47, transcription factor A1, transcription factor E2a
Species: mouse
Products:     Tcf3

Top Publications

  1. Greenbaum S, Lazorchak A, Zhuang Y. Differential functions for the transcription factor E2A in positive and negative gene regulation in pre-B lymphocytes. J Biol Chem. 2004;279:45028-35 pubmed
    The transcription factors encoded by the E2A gene have been shown to play essential roles in the initiation and progression of lymphocyte development...
  2. Greenbaum S, Zhuang Y. Identification of E2A target genes in B lymphocyte development by using a gene tagging-based chromatin immunoprecipitation system. Proc Natl Acad Sci U S A. 2002;99:15030-5 pubmed
    The transcription factors encoded by the E2A gene are known to be essential for B lymphocyte development, and ectopic expression or gene inactivation studies have revealed several potential lineage-specific E2A target genes...
  3. Zhuang Y, Jackson A, Pan L, Shen K, Dai M. Regulation of E2A gene expression in B-lymphocyte development. Mol Immunol. 2004;40:1165-77 pubmed
    Biochemical and genetic studies have demonstrated that transcription factors encoded by the E2A gene are essential in regulating B lineage specific gene expression and B lineage commitment...
  4. Bain G, Maandag E, Izon D, Amsen D, Kruisbeek A, Weintraub B, et al. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell. 1994;79:885-92 pubmed
    E12 and E47 are two helix-loop-helix transcription factors that arise by alternative splicing of the E2A gene. Both have been implicated in the regulation of immunoglobulin gene expression...
  5. Bain G, Engel I, Robanus Maandag E, te Riele H, Voland J, Sharp L, et al. E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas. Mol Cell Biol. 1997;17:4782-91 pubmed
    The E2A gene products, E12 and E47, are critical for proper early B-cell development and commitment to the B-cell lineage. Here we reveal a new role for E2A in T-lymphocyte development...
  6. Yashiro Ohtani Y, He Y, Ohtani T, Jones M, Shestova O, Xu L, et al. Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A. Genes Dev. 2009;23:1665-76 pubmed publisher
    ..We show that Notch1 and E2A directly regulate Notch1 transcription in pre-beta-selected thymocytes...
  7. Scheele J, Kolanczyk M, Gantert M, Zemojtel T, Dorn A, Sykes D, et al. The Spt-Ada-Gcn5-acetyltransferase complex interaction motif of E2a is essential for a subset of transcriptional and oncogenic properties of E2a-Pbx1. Leuk Lymphoma. 2009;50:816-28 pubmed publisher
    The oncogene E2a-Pbx1 is formed by the t(1;19) translocation, which joins the N-terminal transactivation domain of E2a with the C-terminal homeodomain of PBX1...
  8. Cochrane S, Zhao Y, Welner R, Sun X. Balance between Id and E proteins regulates myeloid-versus-lymphoid lineage decisions. Blood. 2009;113:1016-26 pubmed publisher
    ..Conversely, enhancing E-protein activity by expressing a variant of E47 resistant to Id-mediated inhibition prevents the myeloid cell fate while driving B-cell differentiation from ..
  9. Bhalla S, Spaulding C, Brumbaugh R, Zagort D, Massari M, Murre C, et al. differential roles for the E2A activation domains in B lymphocytes and macrophages. J Immunol. 2008;180:1694-703 pubmed
    The E2A gene encodes two E protein/class I basic helix-loop-helix transcription factors, E12 and E47, that are essential for B lymphopoiesis...

More Information

Publications63

  1. Murre C, McCaw P, Vaessin H, Caudy M, Jan L, Jan Y, et al. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989;58:537-44 pubmed
    ..HLH motif), has recently been identified in various proteins, including two that bind to immunoglobulin enhancers (E12 and E47)...
  2. Quong M, Martensson A, Langerak A, Rivera R, Nemazee D, Murre C. Receptor editing and marginal zone B cell development are regulated by the helix-loop-helix protein, E2A. J Exp Med. 2004;199:1101-12 pubmed
    Previous studies have indicated that the E2A gene products are required to initiate B lineage development...
  3. Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao T, Zhuang Y. Regulation of E2A activities by histone acetyltransferases in B lymphocyte development. J Biol Chem. 2003;278:2370-6 pubmed
    Genetic studies have demonstrated that the basic helix-loop-helix protein E2A is an essential transcription factor in B lymphocyte lineage commitment and differentiation...
  4. Kee B, Bain G, Murre C. IL-7Ralpha and E47: independent pathways required for development of multipotent lymphoid progenitors. EMBO J. 2002;21:103-13 pubmed
    Mice that lack the transcription factors encoded by the E2A gene or the receptor for interleukin 7 (IL-7R) have severe overlapping defects in lymphocyte development...
  5. Wojciechowski J, Lai A, Kondo M, Zhuang Y. E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression. J Immunol. 2007;178:5717-26 pubmed
    ..b>E2A and HEB are structurally and functionally related basic helix-loop-helix transcription factors involved in T cell ..
  6. Bain G, Quong M, Soloff R, Hedrick S, Murre C. Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47. J Exp Med. 1999;190:1605-16 pubmed
    The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis...
  7. Nishiyama A, Xin L, Sharov A, Thomas M, Mowrer G, Meyers E, et al. Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell. 2009;5:420-33 pubmed publisher
    ..Of the 50 TFs, Cdx2 provoked the most extensive transcriptome perturbation in ESCs, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. ChIP-Seq revealed that CDX2 binds to promoters of upregulated target genes...
  8. Yi F, Pereira L, Hoffman J, Shy B, Yuen C, Liu D, et al. Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal. Nat Cell Biol. 2011;13:762-70 pubmed publisher
    The co-occupancy of Tcf3 with Oct4, Sox2 and Nanog on embryonic stem cell (ESC) chromatin indicated that Tcf3 has been suggested to play an integral role in a poorly understood mechanism underlying Wnt-dependent stimulation of mouse ESC ..
  9. Zhuang Y, Cheng P, Weintraub H. B-lymphocyte development is regulated by the combined dosage of three basic helix-loop-helix genes, E2A, E2-2, and HEB. Mol Cell Biol. 1996;16:2898-905 pubmed
    B-lymphocyte development requires the basic helix-loop-helix proteins encoded by the E2A gene. In this study, the control mechanism of E2A was further explored by disruption of the E2A-related genes, E2-2 and HEB...
  10. Lazorchak A, Wojciechowski J, Dai M, Zhuang Y. E2A promotes the survival of precursor and mature B lymphocytes. J Immunol. 2006;177:2495-504 pubmed
    The basic helix-loop-helix transcription factor E2A is an essential regulator of B lymphocyte lineage commitment and is required to activate the expression of numerous B lineage-specific genes...
  11. Huang Z, Nie L, Xu M, Sun X. Notch-induced E2A degradation requires CHIP and Hsc70 as novel facilitators of ubiquitination. Mol Cell Biol. 2004;24:8951-62 pubmed
    b>E2A transcription factors, E12 and E47, are important regulators of lymphocyte development...
  12. Seet C, Brumbaugh R, Kee B. Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A. J Exp Med. 2004;199:1689-700 pubmed
    The basic helix-loop-helix transcription factors encoded by the E2A gene function at the apex of a transcriptional hierarchy involving E2A, early B cell factor (EBF), and Pax5, which is essential for B lymphopoiesis...
  13. Miyazaki M, Rivera R, Miyazaki K, Lin Y, Agata Y, Murre C. The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells. Nat Immunol. 2011;12:992-1001 pubmed publisher
    It is established that the transcription factor E2A and its antagonist Id3 modulate the checkpoints consisting of the precursor to the T cell antigen receptor (pre-TCR) and the TCR...
  14. Wu C, Hoffman J, Shy B, Ford E, Fuchs E, Nguyen H, et al. Function of Wnt/?-catenin in counteracting Tcf3 repression through the Tcf3-?-catenin interaction. Development. 2012;139:2118-29 pubmed publisher
    ..In contrast to ?-catenin-dependent functions described for Tcf1, Tcf4 and Lef1, the known embryonic functions for Tcf3 in mice, frogs and fish are consistent with ?-catenin-independent repressor activity...
  15. Ikawa T, Kawamoto H, Wright L, Murre C. Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent. Immunity. 2004;20:349-60 pubmed
    ..Enforced expression of E47 in E2A-deficient hematopoietic progenitor cells directly activates the transcription of a subset of B lineage-..
  16. Bain G, Robanus Maandag E, te Riele H, Feeney A, Sheehy A, Schlissel M, et al. Both E12 and E47 allow commitment to the B cell lineage. Immunity. 1997;6:145-54 pubmed
    The E2A gene products, E12 and E47, are required for proper B cell development. Mice lacking the E2A gene products generate only a very small number of B220+ cells, which lack immunoglobulin DJ(H) rearrangements...
  17. Sayegh C, Quong M, Agata Y, Murre C. E-proteins directly regulate expression of activation-induced deaminase in mature B cells. Nat Immunol. 2003;4:586-93 pubmed
    ..Taken together, our observations link helix-loop-helix activity and Aicda gene expression in a common pathway, in which E-protein activity is required for the efficient induction of Aicda transcription. ..
  18. Lin H, Grosschedl R. Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature. 1995;376:263-7 pubmed
  19. Jones M, Kondo M, Zhuang Y. A tamoxifen inducible knock-in allele for investigation of E2A function. BMC Dev Biol. 2009;9:51 pubmed publisher
    ..was created by inserting a tamoxifen-responsive region of the estrogen receptor (ER) at the carboxyl end of the tcfe2a gene to generate E2AER fusion proteins...
  20. Nguyen H, Merrill B, Polak L, Nikolova M, Rendl M, Shaver T, et al. Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia. Nat Genet. 2009;41:1068-75 pubmed publisher
    ..We have discovered that embryonic progenitor cells and postnatal hair follicle stem cells coexpress Tcf3 and Tcf4, which can act as transcriptional activators or repressors...
  21. Yang Q, Kardava L, St Leger A, Martincic K, Varnum Finney B, Bernstein I, et al. E47 controls the developmental integrity and cell cycle quiescence of multipotential hematopoietic progenitors. J Immunol. 2008;181:5885-94 pubmed
    ..Herein, we show that multipotent LSKs (lineage(-)Sca(high)c-kit(+)) from E47-deficient mice exhibit a striking hyperproliferation associated with a loss of cell cycle quiescence and increased ..
  22. Ikawa T, Kawamoto H, Goldrath A, Murre C. E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J Exp Med. 2006;203:1329-42 pubmed
    The helix-loop-helix protein, E47, is essential for both B- and T-lineage development...
  23. Dias S, Mansson R, Gurbuxani S, Sigvardsson M, Kee B. E2A proteins promote development of lymphoid-primed multipotent progenitors. Immunity. 2008;29:217-27 pubmed publisher
    ..Here, we demonstrated that the E2A transcription factors were required for proper development of LMPPs...
  24. Jones Mason M, Zhao X, Kappes D, Lasorella A, Iavarone A, Zhuang Y. E protein transcription factors are required for the development of CD4(+) lineage T cells. Immunity. 2012;36:348-61 pubmed publisher
    ..transition during T cell development is initiated by downregulation of the E protein transcription factors HEB and E2A. Here, we have demonstrated that in addition to regulating the onset of this transition, HEB and E2A also play a ..
  25. Wray J, Kalkan T, Gómez López S, Eckardt D, Cook A, Kemler R, et al. Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation. Nat Cell Biol. 2011;13:838-45 pubmed publisher
    ..However, requirement for Gsk3 inhibition is dictated by expression of T-cell factor 3 (Tcf3) and mediated by direct interaction with β-catenin...
  26. D Cruz L, Knell J, Fujimoto J, Goldrath A. An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells. Nat Immunol. 2010;11:240-9 pubmed publisher
    ..Thus, our results show that HEB is a specific and essential factor in T cell development and in the generation of the iNKT cell lineage, defining a unique role for HEB in the regulation of lymphocyte maturation. ..
  27. Cai Y, Xu Z, Xie J, Ham A, Koury M, Hiebert S, et al. Eto2/MTG16 and MTGR1 are heteromeric corepressors of the TAL1/SCL transcription factor in murine erythroid progenitors. Biochem Biophys Res Commun. 2009;390:295-301 pubmed publisher
    ..These results identify Eto2 and Mtgr1 as authentic interaction partners of Tal1 and suggest they act as heteromeric corepressors of this bHLH transcription factor during erythroid differentiation. ..
  28. Pan L, Hanrahan J, Li J, Hale L, Zhuang Y. An analysis of T cell intrinsic roles of E2A by conditional gene disruption in the thymus. J Immunol. 2002;168:3923-32 pubmed
    The importance of E2A transcription factors in T cell development has been demonstrated in studies of E2A-deficient mice, which display abnormal T cell development and a high frequency of T cell lymphomas...
  29. DeKoter R, Lee H, Singh H. PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors. Immunity. 2002;16:297-309 pubmed
    ..1 in early B cell development, it is not required. These results demonstrate that PU.1 functions to regulate early B cell development in part by controlling the expression of the IL-7Ralpha gene. ..
  30. Perez Moreno M, Locascio A, Rodrigo I, Dhondt G, Portillo F, Nieto M, et al. A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions. J Biol Chem. 2001;276:27424-31 pubmed
    ..Here we show that the mouse E12/E47 basic helix-loop-helix transcription factor (the E2A gene product) acts as a repressor of E-cadherin expression and ..
  31. Frasca D, Nguyen D, Riley R, Blomberg B. Decreased E12 and/or E47 transcription factor activity in the bone marrow as well as in the spleen of aged mice. J Immunol. 2003;170:719-26 pubmed
    The E2A-encoded transcription factors E12 and E47 are key regulators of B cell functions...
  32. Engel I, Murre C. E2A proteins enforce a proliferation checkpoint in developing thymocytes. EMBO J. 2004;23:202-11 pubmed
    ..Furthermore, we demonstrate that E47 can act in concert with Bcl-2 to induce cell-cycle arrest in vitro...
  33. Yan W, Young A, Soares V, Kelley R, Benezra R, Zhuang Y. High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice. Mol Cell Biol. 1997;17:7317-27 pubmed
    The basic-helix-loop-helix (bHLH) proteins encoded by the E2A gene are broadly expressed transcription regulators which function through binding to the E-box enhancer sequences...
  34. Semerad C, Mercer E, Inlay M, Weissman I, Murre C. E2A proteins maintain the hematopoietic stem cell pool and promote the maturation of myelolymphoid and myeloerythroid progenitors. Proc Natl Acad Sci U S A. 2009;106:1930-5 pubmed publisher
    ..Pre CFU-E, Pre GM, MkP, and granulocyte-macrophage compartments were all significantly reduced in E2A-deficient bone marrow...
  35. Bain G, Romanow W, Albers K, Havran W, Murre C. Positive and negative regulation of V(D)J recombination by the E2A proteins. J Exp Med. 1999;189:289-300 pubmed
    ..Here we show that the E2A gene products are essential for the proper coordinated temporal regulation of V(D)J rearrangements within the T ..
  36. Jones M, Zhuang Y. Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors. Immunity. 2007;27:860-70 pubmed
    ..We have shown here that the structurally and functionally related transcription factors HEB and E2A work together to maintain DP fate and to control the DP to SP transition...
  37. O RIORDAN M, Grosschedl R. Coordinate regulation of B cell differentiation by the transcription factors EBF and E2A. Immunity. 1999;11:21-31 pubmed
    The transcription factors EBF and E2A are required at a similar step in early B cell differentiation. EBF and E2A synergistically upregulate transcription of endogenous B cell-specific genes in a non-B cell line...
  38. Agata Y, Tamaki N, Sakamoto S, Ikawa T, Masuda K, Kawamoto H, et al. Regulation of T cell receptor beta gene rearrangements and allelic exclusion by the helix-loop-helix protein, E47. Immunity. 2007;27:871-84 pubmed
    ..Here, we demonstrated that the basic helix-loop-helix protein, E47, promoted T cell receptor beta (TCRbeta) gene rearrangement by directly binding to target gene segments to increase ..
  39. Kee B, Rivera R, Murre C. Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-beta. Nat Immunol. 2001;2:242-7 pubmed
    ..Our data show a key role for E proteins in lymphocyte survival and link the activity of E proteins, and their antagonists, to members of the TGF-beta family of cytokines. ..
  40. Tremblay M, Herblot S, Lecuyer E, Hoang T. Regulation of pT alpha gene expression by a dosage of E2A, HEB, and SCL. J Biol Chem. 2003;278:12680-7 pubmed
    ..We have shown that the transcription factors E2A and HEB associate with high affinity to these E-boxes...
  41. Maruyama T, Li J, Vaque J, Konkel J, Wang W, Zhang B, et al. Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3. Nat Immunol. 2011;12:86-95 pubmed publisher
    ..Enhanced binding of the transcription factor E2A to the Foxp3 promoter promoted Foxp3 transcription...
  42. Lazorchak A, Schlissel M, Zhuang Y. E2A and IRF-4/Pip promote chromatin modification and transcription of the immunoglobulin kappa locus in pre-B cells. Mol Cell Biol. 2006;26:810-21 pubmed
    ..b>E2A transcription factors have been indicated to be directly involved in the regulation of Igkappa locus activation...
  43. Borghesi L, Aites J, Nelson S, Lefterov P, James P, Gerstein R. E47 is required for V(D)J recombinase activity in common lymphoid progenitors. J Exp Med. 2005;202:1669-77 pubmed
    ..Here, we show that loss of the transcription factor E47 produces a reduced CLP population that lacks V(D)J recombinase activity and D-J(H) rearrangements in vivo...
  44. Maier H, Ostraat R, Gao H, Fields S, Shinton S, Medina K, et al. Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat Immunol. 2004;5:1069-77 pubmed
    ..EBF and the basic helix-loop-helix transcription factor E47 each contributed to epigenetic modifications of the mb-1 promoter, including CpG demethylation and nucleosomal ..
  45. Beck K, Peak M, Ota T, Nemazee D, Murre C. Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci. J Exp Med. 2009;206:2271-84 pubmed publisher
    The E2A gene products, E12 and E47, are critical regulators of B cell development. However, it remains elusive whether E12 and E47 have overlapping and/or distinct functions during B lymphopoiesis...
  46. Zhuang Y, Barndt R, Pan L, Kelley R, Dai M. Functional replacement of the mouse E2A gene with a human HEB cDNA. Mol Cell Biol. 1998;18:3340-9 pubmed
    ..mammalian development, we generated and tested a panel of E2A knockin mutations including subtle mutations in the E12 and E47 exons and substitution of both E12 and E47 exons with a human HEB cDNA...
  47. Sigvardsson M, Clark D, Fitzsimmons D, Doyle M, Akerblad P, Breslin T, et al. Early B-cell factor, E2A, and Pax-5 cooperate to activate the early B cell-specific mb-1 promoter. Mol Cell Biol. 2002;22:8539-51 pubmed
    ..In addition to EBF and Pax-5 binding sites, we detected occupancy of a consensus binding site for E2A proteins (E box) in pre-B cells...
  48. Boos M, Yokota Y, Eberl G, Kee B. Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J Exp Med. 2007;204:1119-30 pubmed
    ..define the mechanism by which Id2 functions by showing that a reduction in E protein activity, through deletion of E2A, overcomes the need for Id2 in development of BM mNK cells, LTi cells, and secondary lymphoid tissues...
  49. Zhuang Y, Soriano P, Weintraub H. The helix-loop-helix gene E2A is required for B cell formation. Cell. 1994;79:875-84 pubmed
    Heterodimers between tissue-specific basic-helix-loop-helix proteins and the gene products of E2A play major roles in determining tissue-specific cell fate...
  50. Solberg N, Machon O, Krauss S. Characterization and functional analysis of the 5'-flanking promoter region of the mouse Tcf3 gene. Mol Cell Biochem. 2012;360:289-99 pubmed publisher
    b>Tcf3 is a nuclear mediator of canonical Wnt signaling which functions in many systems as a repressor of target gene transcription. In this study, we have cloned and characterized a 6...
  51. Solberg N, Machon O, Machonova O, Krauss S. Mouse Tcf3 represses canonical Wnt signaling by either competing for ?-catenin binding or through occupation of DNA-binding sites. Mol Cell Biochem. 2012;365:53-63 pubmed publisher
    b>Tcf3 acts as a transcription factor controlling gene expression in canonical Wnt signaling. In this study we show that mouse Tcf3 represses canonical Wnt signaling in mouse neural stem cells and in human HEK 293 cells...
  52. Kwon K, Hutter C, Sun Q, Bilic I, Cobaleda C, Malin S, et al. Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development. Immunity. 2008;28:751-62 pubmed publisher
    The transcription factor E2A controls the initiation of B lymphopoiesis, which is arrested at the pre-pro-B cell stage in E2A-deficient mice...
  53. Nakayama H, Scott I, Cross J. The transition to endoreduplication in trophoblast giant cells is regulated by the mSNA zinc finger transcription factor. Dev Biol. 1998;199:150-63 pubmed
    ..Together, these data suggest that mSNA has an ESCARGOT-like function to repress the transcription of genes that promote the transition from mitotic to endoreduplicative cell cycles in rodent trophoblast. ..
  54. Nie L, Perry S, Zhao Y, Huang J, Kincade P, Farrar M, et al. Regulation of lymphocyte development by cell-type-specific interpretation of Notch signals. Mol Cell Biol. 2008;28:2078-90 pubmed publisher
    ..activation accelerates ubiquitin-mediated and mitogen-activated protein kinase (MAPK)-dependent degradation of E2A transcription factors and Janus kinases, molecules essential for both B- and T-lymphocyte development...