Genomes and Genes
Gene Symbol: Tcf3
Description: transcription factor 3
Alias: Pan2, Tcfe2a, transcription factor E2-alpha, TCF-3, immunoglobulin enhancer-binding factor E12/E47, pancreas specific transcription factor 1c, transcription factor E2a, transcription factor E2a-like, transcription regulator Pan
- Landry J, Kinston S, Knezevic K, de Bruijn M, Wilson N, Nottingham W, et al. Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver. Blood. 2008;111:3005-14 pubmed publisher..Together, our data provide a key component of the transcriptional network of early hematopoiesis by identifying downstream targets of Scl that can explain key aspects of the early Scl(-/-) phenotype...
- Muir T, Sadler Riggleman I, Skinner M. Role of the basic helix-loop-helix transcription factor, scleraxis, in the regulation of Sertoli cell function and differentiation. Mol Endocrinol. 2005;19:2164-74 pubmed..This is one of the first adult and nontendon/chondrocyte-associated functions described for scleraxis. ..
- Lejard V, Brideau G, Blais F, Salingcarnboriboon R, Wagner G, Roehrl M, et al. Scleraxis and NFATc regulate the expression of the pro-alpha1(I) collagen gene in tendon fibroblasts. J Biol Chem. 2007;282:17665-75 pubmed..Taken together, these results suggest that SCX and NFATc4 cooperate to activate the COL1a1 gene specifically in tendon fibroblasts. ..
- Ikawa T, Kawamoto H, Wright L, Murre C. Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent. Immunity. 2004;20:349-60 pubmed..These observations indicate that E2A-deficient hematopoietic progenitor cells remain pluripotent after long-term culture in vitro and that E2A proteins play a critical role in B cell commitment. ..
- Zhang W, Yi M, Chen X, Cole F, Krauss R, Kang J. Cortical thinning and hydrocephalus in mice lacking the immunoglobulin superfamily member CDO. Mol Cell Biol. 2006;26:3764-72 pubmed..These results indicate that CDO promotes neuronal differentiation and support the hypothesis that CDO coordinates differentiation of multiple cell lineages by regulating the activity of tissue-specific bHLH factors. ..
- Kang J, Yi M, Zhang W, Feinleib J, Cole F, Krauss R. Netrins and neogenin promote myotube formation. J Cell Biol. 2004;167:493-504 pubmed..It is proposed that netrin-3 and neogenin may promote myogenic differentiation by an autocrine mechanism as components of a higher order complex of several promyogenic cell surface proteins. ..
- Knöfler M, Meinhardt G, Bauer S, Loregger T, Vasicek R, Bloor D, et al. Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains. Biochem J. 2002;361:641-51 pubmed..Furthermore, the data suggest that Hand1 can act as a repressor by two independent mechanisms; sequestration of class A bHLH factors from E-boxes and inhibition of their transcriptional activity. ..
- Jia J, Dai M, Zhuang Y. E proteins are required to activate germline transcription of the TCR Vbeta8.2 gene. Eur J Immunol. 2008;38:2806-20 pubmed publisher..2 germline transcription. We provide evidence that IL-7R expression is only partially controlled by E2A, suggesting a role for E2A in driving Vbeta8.2 germline transcription independent of IL-7R activation. ..
- Siu M, Chen W, Tsai H, Chen H, Yin J, Chen C, et al. TCF7 is suppressed by the androgen receptor via microRNA-1-mediated downregulation and is involved in the development of resistance to androgen deprivation in prostate cancer. Prostate Cancer Prostatic Dis. 2017;20:172-178 pubmed publisher..Dysregulation of TCF7 promoted a survival advantage and resistance to androgen deprivation, suggesting its therapeutic potential for castration-resistant prostate cancer. ..
- Metz R, Ziff E. The helix-loop-helix protein rE12 and the C/EBP-related factor rNFIL-6 bind to neighboring sites within the c-fos serum response element. Oncogene. 1991;6:2165-78 pubmed
- Holler K, Hendershot T, Troy S, Vincentz J, Firulli A, Howard M. Targeted deletion of Hand2 in cardiac neural crest-derived cells influences cardiac gene expression and outflow tract development. Dev Biol. 2010;341:291-304 pubmed publisher..Our genetic model has made it possible to investigate the molecular genetics of neural crest contributions to outflow tract morphogenesis and cell differentiation. ..
- Pedraza N, Rafel M, Navarro I, Encinas M, Aldea M, Gallego C. Mixed lineage kinase phosphorylates transcription factor E47 and inhibits TrkB expression to link neuronal death and survival pathways. J Biol Chem. 2009;284:32980-8 pubmed publisher..This molecular link would explain why MLK inhibitors not only prevent activation of cell death processes but also enhance cell survival signaling as a key aspect of their neuroprotective potential. ..
- Sommer L, Hagenbuchle O, Wellauer P, Strubin M. Nuclear targeting of the transcription factor PTF1 is mediated by a protein subunit that does not bind to the PTF1 cognate sequence. Cell. 1991;67:987-94 pubmed..However, if beta is coinjected with purified 75 kd protein or a particular size fraction of pancreatic mRNA, it can be converted to alpha and imported into the nucleus. ..
- Black B, Ligon K, Zhang Y, Olson E. Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family. J Biol Chem. 1996;271:26659-63 pubmed..These results suggest that members of the MEF2 family perform similar roles in synergistic activation of transcription in myogenic and neurogenic lineages by serving as cofactors for cell type-specific bHLH proteins. ..
- 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. ..
- Thomas M, Yao K, Tenser M, Wong G, Habener J. Bridge-1, a novel PDZ-domain coactivator of E2A-mediated regulation of insulin gene transcription. Mol Cell Biol. 1999;19:8492-504 pubmed..Bridge-1, by utilizing its PDZ-like domain to interact with E12, may provide a new mechanism for the coactivation and regulation of transcription of the insulin gene. ..
- 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. ..
- El Ghouzzi V, Legeai Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, et al. Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location. Hum Mol Genet. 2000;9:813-9 pubmed..We conclude that at least two distinct mechanisms account for loss of TWIST protein function in SCS patients, namely protein degradation and subcellular mislocalization. ..
- Bayne R, Martins da Silva S, Anderson R. Increased expression of the FIGLA transcription factor is associated with primordial follicle formation in the human fetal ovary. Mol Hum Reprod. 2004;10:373-81 pubmed..Similar mobility shifts were identified in human fetal ovary extracts. These results suggest that FIGLA is involved in continued oocyte survival as primordial follicles form in the human as in the rodent ovary. ..
- 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..Finally, we provide genetic evidence in the mouse that E2A gene dosage can influence the development of pre-B cells during the phase of Igkappa gene activation. ..
- Masui T, Long Q, Beres T, Magnuson M, Macdonald R. Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex. Genes Dev. 2007;21:2629-43 pubmed..Action within an organ-specific transcription factor is a previously unknown function for RBPJ and is independent of its role in Notch signaling. ..
- Carlberg A, Tuan R, Hall D. Regulation of scleraxis function by interaction with the bHLH protein E47. Mol Cell Biol Res Commun. 2000;3:82-6 pubmed..Further, when expressed together, scleraxis and E47 synergistically enhanced transcription from a promoter containing multiple E-box binding sites. ..
- O Neil J, Billa M, Oikemus S, Kelliher M. The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice. Oncogene. 2001;20:3897-905 pubmed..Our study suggests that the bHLH protein tal-1 contributes to leukemia by interfering with E2A protein function(s). ..
- Wang Z, Kim J, Teng Y, Ding H, Zhang J, Hai T, et al. Loss of ATF3 promotes hormone-induced prostate carcinogenesis and the emergence of CK5(+)CK8(+) epithelial cells. Oncogene. 2016;35:3555-64 pubmed publisher..Consistent with these findings, low ATF3 expression was found to be a poor prognostic marker for prostate cancer in a cohort of 245 patients. Our results thus support that ATF3 is a tumor suppressor in prostate cancer. ..
- Heng J, Tan S. Cloning and characterization of GRIPE, a novel interacting partner of the transcription factor E12 in developing mouse forebrain. J Biol Chem. 2002;277:43152-9 pubmed..Taken together, these results indicate that GRIPE is a novel protein dimerization of which with E12 has important consequences for cells undergoing neuronal differentiation. ..
- Kho C, Huggins G, Endege W, Hsieh C, Lee M, Haber E. Degradation of E2A proteins through a ubiquitin-conjugating enzyme, UbcE2A. J Biol Chem. 1997;272:3845-51 pubmed..Finally, antisense UbcE2A reduces E12 degradation. By participating in the degradation of the E2A proteins, UbcE2A may regulate cell growth and differentiation. ..
- 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..Our findings redefine the essential functions of Id2 in lymphoid development and provide insight into the dynamic regulation of E and Id proteins during this process. ..
- Huang A, Zhao H, Quan Y, Jin R, Feng B, Zheng M. E2A predicts prognosis of colorectal cancer patients and regulates cancer cell growth by targeting miR-320a. PLoS ONE. 2014;9:e85201 pubmed publisher..E2A is an independent prognostic factor for CRC patients and targets miR-320a to regulate cell proliferation of colon cancer cells. ..
- Liu A, Desai B, Stoffers D. Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity. Mol Cell Biol. 2004;24:4372-83 pubmed..The coexpression of PCIF1 with PDX-1 in beta cells and the ability of PCIF1 to repress PDX-1 transactivation suggest that modulation of PDX-1 function by PCIF1 may regulate normal beta cell differentiation. ..
- Barndt R, Dai M, Zhuang Y. Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant negative mutation of HEB. Mol Cell Biol. 2000;20:6677-85 pubmed..These results indicate that E2A-HEB heterodimers play obligatory roles both before and after TCRbeta gene rearrangement during the alpha/beta lineage T-cell development. ..
- Ou S, García Martínez L, Paulssen E, Gaynor R. Role of flanking E box motifs in human immunodeficiency virus type 1 TATA element function. J Virol. 1994;68:7188-99 pubmed
- Furumatsu T, Shukunami C, Amemiya Kudo M, Shimano H, Ozaki T. Scleraxis and E47 cooperatively regulate the Sox9-dependent transcription. Int J Biochem Cell Biol. 2010;42:148-56 pubmed publisher..These findings suggest that Scx and E47 might modulate the primary chondrogenesis by associating with the Sox9-related transcriptional complex, and by binding to the conserved E-box on Col2a1 promoter. ..
- Malecki M, Jhala U, Antonellis A, Fields L, Doria A, Orban T, et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet. 1999;23:323-8 pubmed..Our findings suggest that deficient binding of NEUROD1 or binding of a transcriptionally inactive NEUROD1 polypeptide to target promoters in pancreatic islets leads to the development of type 2 diabetes in humans. ..
- Morin S, Pozzulo G, Robitaille L, Cross J, Nemer M. MEF2-dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters. J Biol Chem. 2005;280:32272-8 pubmed..These findings identify a novel mechanism for HAND action in the heart and provide a general paradigm to understand the mechanism of HAND action in organogenesis. ..
- Hill A, Riley P. Differential regulation of Hand1 homodimer and Hand1-E12 heterodimer activity by the cofactor FHL2. Mol Cell Biol. 2004;24:9835-47 pubmed
- Smith S, Watada H, German M. Neurogenin3 activates the islet differentiation program while repressing its own expression. Mol Endocrinol. 2004;18:142-9 pubmed..In summary, while Neurogenin3 orchestrates islet cell differentiation by activating islet cell transcription factor genes, it simultaneously represses its own promoter. ..
- Dai Y, Cserjesi P. The basic helix-loop-helix factor, HAND2, functions as a transcriptional activator by binding to E-boxes as a heterodimer. J Biol Chem. 2002;277:12604-12 pubmed..We conclude that HAND2 functions as a transcription activator by binding a subset of E-boxes as a heterodimer with E-proteins. ..
- Gazit R, Krizhanovsky V, Ben Arie N. Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway. Development. 2004;131:903-13 pubmed..Taken together, our data demonstrate that CGC differentiation, but not specification, depends on Math1, which acts by regulating the level of multiple components of the Notch signaling pathway. ..
- Loveys D, Streiff M, Kato G. E2A basic-helix-loop-helix transcription factors are negatively regulated by serum growth factors and by the Id3 protein. Nucleic Acids Res. 1996;24:2813-20 pubmed..These observations extend the role of Id3 in the functional antagonism of E2A-class transcription factors, and suggest that E2A proteins may mediate growth inhibition. ..
- Chervinsky D, Zhao X, Lam D, Ellsworth M, Gross K, Aplan P. Disordered T-cell development and T-cell malignancies in SCL LMO1 double-transgenic mice: parallels with E2A-deficient mice. Mol Cell Biol. 1999;19:5025-35 pubmed
- Sun T, Dong H, Wu L, Kane M, Rowitch D, Stiles C. Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors in developing neural tube associated with formation of a specific physical complex. J Neurosci. 2003;23:9547-56 pubmed..2 that helps to establish the pMN-p3 boundary in the developing spinal cord. ..
- Murakami M, Kataoka K, Tominaga J, Nakagawa O, Kurihara H. Differential cooperation between dHAND and three different E-proteins. Biochem Biophys Res Commun. 2004;323:168-74 pubmed..By contrast, little signal was detected in the heart, suggesting that dHAND complexes with partners other than E-proteins in cardiac tissue. ..
- Yoon S, Wills A, Chuong E, Gupta R, Baker J. HEB and E2A function as SMAD/FOXH1 cofactors. Genes Dev. 2011;25:1654-61 pubmed publisher..Taken together, E proteins are novel Nodal signaling cofactors that associate with SMAD2/3 and FOXH1 and are necessary for mesendoderm differentiation. ..
- Joshi K, Lee S, Lee B, Lee J, Lee S. LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons. Neuron. 2009;61:839-51 pubmed publisher..Thus, LMO4 plays essential roles in directing a balanced generation of inhibitory and excitatory neurons in the ventral spinal cord. ..
- 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..Collectively, these results suggest that E2A and HATs collaboratively regulate B cell development. ..
- Lu J, Richardson J, Olson E. Capsulin: a novel bHLH transcription factor expressed in epicardial progenitors and mesenchyme of visceral organs. Mech Dev. 1998;73:23-32 pubmed
- Muir T, Wilson Rawls J, Stevens J, Rawls A, Schweitzer R, Kang C, et al. Integration of CREB and bHLH transcriptional signaling pathways through direct heterodimerization of the proteins: role in muscle and testis development. Mol Reprod Dev. 2008;75:1637-52 pubmed publisher..The observations suggest a mechanism for direct cross-talk between cAMP induced and bHLH controlled cellular differentiation...
- Espira L, Lamoureux L, Jones S, Gerard R, Dixon I, Czubryt M. The basic helix-loop-helix transcription factor scleraxis regulates fibroblast collagen synthesis. J Mol Cell Cardiol. 2009;47:188-95 pubmed publisher..These data support a novel and previously unknown role for scleraxis in the regulation of collagen gene expression in the heart, including in post-infarct scar formation. ..
- McFadden D, McAnally J, Richardson J, Charité J, Olson E. Misexpression of dHAND induces ectopic digits in the developing limb bud in the absence of direct DNA binding. Development. 2002;129:3077-88 pubmed..These findings suggest that dHAND may act via novel transcriptional mechanisms mediated by protein-protein interactions independent of direct DNA binding. ..
- Vinals F, Ventura F. Myogenin protein stability is decreased by BMP-2 through a mechanism implicating Id1. J Biol Chem. 2004;279:45766-72 pubmed..Our findings indicate that induction of Id1 not only blocks transcriptional activity but also induces myogenin degradation by blocking formation of myogenin-E47 protein complexes. ..
- Ravanpay A, Olson J. E protein dosage influences brain development more than family member identity. J Neurosci Res. 2008;86:1472-81 pubmed publisher..These findings, together with homology in the primary peptide sequence of E proteins, suggest functional compensation among E proteins during development of the nervous system. ..
- Udayakumar T, Stoyanova R, Shareef M, Mu Z, Philip S, Burnstein K, et al. Edelfosine Promotes Apoptosis in Androgen-Deprived Prostate Tumors by Increasing ATF3 and Inhibiting Androgen Receptor Activity. Mol Cancer Ther. 2016;15:1353-63 pubmed publisher..Edelfosine shows promise in combination with AD for the treatment of prostate cancer patients. Mol Cancer Ther; 15(6); 1353-63. Â©2016 AACR. ..
- Schlaeger T, Schuh A, Flitter S, Fisher A, Mikkola H, Orkin S, et al. Decoding hematopoietic specificity in the helix-loop-helix domain of the transcription factor SCL/Tal-1. Mol Cell Biol. 2004;24:7491-502 pubmed..Our data highlight the functional complexity of bHLH proteins, provide mechanistic insight into SCL function, and strongly support the existence of an active SCL/LMO2-containing multiprotein complex in early hematopoietic cells. ..
- Li C, Cai S, Wang X, Jiang Z. Hypomethylation-associated up-regulation of TCF3 expression and recurrence in stage II and III colorectal cancer. PLoS ONE. 2014;9:e112005 pubmed publisherTranscription factor 3 (TCF3) implicates Wnt signaling pathway and regulates E-cadherin expression, which is involved in aggressiveness of tumors...
- Chaudhary J, Skinner M. Role of the transcriptional coactivator CBP/p300 in linking basic helix-loop-helix and CREB responses for follicle-stimulating hormone-mediated activation of the transferrin promoter in Sertoli cells. Biol Reprod. 2001;65:568-74 pubmed..These observations suggest that CBP/p300 appears to be involved in regulating FSH-mediated activation of the transferrin promoter by linking bHLH and CREB activities. ..
- Kim J, Chu K, Kim H, Seong H, Park K, Sanyal S, et al. Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD. Mol Endocrinol. 2004;18:776-90 pubmed
- Turunen M, Dunlop T, Carlberg C, Väisänen S. Selective use of multiple vitamin D response elements underlies the 1 alpha,25-dihydroxyvitamin D3-mediated negative regulation of the human CYP27B1 gene. Nucleic Acids Res. 2007;35:2734-47 pubmed..This data explains, in part, why the human CYP27B1 gene is repressed in HEK-293 but not in MCF-7 cells. ..
- Henthorn P, Kiledjian M, Kadesch T. Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. Science. 1990;247:467-70 pubmed..The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation. ..
- Zhao F, Vilardi A, Neely R, Choi J. Promotion of cell cycle progression by basic helix-loop-helix E2A. Mol Cell Biol. 2001;21:6346-57 pubmed..The induction of some cyclin transcripts occurred even in the absence of protein synthesis. We conclude that, in some cells, E2A can promote cell cycle progression, contrary to the present view that E2A inhibits G(1) progression. ..
- Nelson C, Shen L, Meister A, Fodor E, Rutter W. Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs. Genes Dev. 1990;4:1035-43 pubmed..The Pan/E12,E47 proteins also show structural similarity with the Drosophila daughterless protein, MyoD, Myogenin, and Myf-5. ..
- Funato N, Ohyama K, Kuroda T, Nakamura M. Basic helix-loop-helix transcription factor epicardin/capsulin/Pod-1 suppresses differentiation by negative regulation of transcription. J Biol Chem. 2003;278:7486-93 pubmed..These results indicate that epicardin/capsulin/Pod-1 functions as a negative regulator of differentiation of myoblasts through transcription in at least two distinct steps, cell growth arrest and lineage-specific differentiation. ..
- 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..Together, our studies demonstrate the complexity of factors regulating tissue-specific transcription and support the concept that EBF, E2A, and Pax-5 cooperate to activate target genes in early B-cell development. ..