Ets1

Summary

Gene Symbol: Ets1
Description: E26 avian leukemia oncogene 1, 5' domain
Alias: AI196000, AI448617, D230050P06, Ets-1, Tpl1, protein C-ets-1, avian erythroblastosis virus E26 oncogene 1, p54, tumor progression locus 1
Species: mouse
Products:     Ets1

Top Publications

  1. Bellacosa A, Datta K, Bear S, Patriotis C, Lazo P, Copeland N, et al. Effects of provirus integration in the Tpl-1/Ets-1 locus in Moloney murine leukemia virus-induced rat T-cell lymphomas: levels of expression, polyadenylation, transcriptional initiation, and differential splicing of the Ets-1 mRNA. J Virol. 1994;68:2320-30 pubmed
  2. Mucci N, Ianni A, Ursini C, Arzani D, Bhat N, Navarra P, et al. In vivo modulation of ETS genes induced by electromagnetic fields. In Vivo. 2001;15:489-94 pubmed
    We have previously shown that electromagnetic field (EMF) exposure induces ETS1 oncogene overexpression in different cell lines...
  3. Wang D, John S, Clements J, Percy D, Barton K, Garrett Sinha L. Ets-1 deficiency leads to altered B cell differentiation, hyperresponsiveness to TLR9 and autoimmune disease. Int Immunol. 2005;17:1179-91 pubmed
    ..Hence, our studies establish Ets-1 as an important regulator of peripheral B cell differentiation and B cell responses to TLR9 activation. ..
  4. Clements J, John S, Garrett Sinha L. Impaired generation of CD8+ thymocytes in Ets-1-deficient mice. J Immunol. 2006;177:905-12 pubmed
    ..These data identify Ets-1 as a key transcription factor regulating thymocyte positive selection and lineage commitment of MHC class I-restricted thymocytes. ..
  5. Higuchi T, Bartel F, Masuya M, Deguchi T, Henderson K, Li R, et al. Thymomegaly, microsplenia, and defective homeostatic proliferation of peripheral lymphocytes in p51-Ets1 isoform-specific null mice. Mol Cell Biol. 2007;27:3353-66 pubmed
    b>Ets1 is a member of the Ets transcription factor family. Alternative splicing of exon VII results in two naturally occurring protein isoforms: full-length Ets1 (p51-Ets1) and Ets1(DeltaVII) (p42-Ets1)...
  6. Nagarajan P, Parikh N, Garrett Sinha L, Sinha S. Ets1 induces dysplastic changes when expressed in terminally-differentiating squamous epidermal cells. PLoS ONE. 2009;4:e4179 pubmed publisher
    b>Ets1 is an oncogene that functions as a transcription factor and regulates the activity of many genes potentially important for tumor initiation and progression...
  7. Moisan J, Grenningloh R, Bettelli E, Oukka M, Ho I. Ets-1 is a negative regulator of Th17 differentiation. J Exp Med. 2007;204:2825-35 pubmed
    ..Based on these observations, we report that Ets-1 is a negative regulator of Th17 differentiation. ..
  8. Grenningloh R, Kang B, Ho I. Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory responses. J Exp Med. 2005;201:615-26 pubmed
    ..In addition, Ets-1-deficient Th1 cells also produce a very high level of interleukin 10. Thus, Ets-1 plays a crucial and unique role in the reciprocal regulation of inflammatory and antiinflammatory Th responses. ..
  9. Wei G, Srinivasan R, Cantemir Stone C, Sharma S, Santhanam R, Weinstein M, et al. Ets1 and Ets2 are required for endothelial cell survival during embryonic angiogenesis. Blood. 2009;114:1123-30 pubmed publisher
    ..Transcription factors Ets1 and Ets2 are targets of ras/Erk signaling pathways that have been implicated in endothelial cell function in vitro, ..

More Information

Publications62

  1. Nagarajan P, Chin S, Wang D, Liu S, Sinha S, Garrett Sinha L. Ets1 blocks terminal differentiation of keratinocytes and induces expression of matrix metalloproteases and innate immune mediators. J Cell Sci. 2010;123:3566-75 pubmed publisher
    The transcription factor Ets1 is normally expressed in the proliferative layer of stratified epithelium, but expression of Ets1 is significantly upregulated in squamous cell carcinomas...
  2. Anderson M, Hernandez Hoyos G, Diamond R, Rothenberg E. Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development. 1999;126:3131-48 pubmed
  3. Barton K, Muthusamy N, Fischer C, Ting C, Walunas T, Lanier L, et al. The Ets-1 transcription factor is required for the development of natural killer cells in mice. Immunity. 1998;9:555-63 pubmed
    ..Thus, Ets-1 defines a novel transcriptional pathway that is required for the development of the NK cell lineage in mice. ..
  4. Slupsky C, Gentile L, Donaldson L, Mackereth C, Seidel J, Graves B, et al. Structure of the Ets-1 pointed domain and mitogen-activated protein kinase phosphorylation site. Proc Natl Acad Sci U S A. 1998;95:12129-34 pubmed
    ..These results suggest that the Ets-1 PNT domain functions in heterotypic protein interactions and support the possibility that target recognition is coupled to structuring of the MAP kinase site. ..
  5. Eyquem S, Chemin K, Fasseu M, Bories J. The Ets-1 transcription factor is required for complete pre-T cell receptor function and allelic exclusion at the T cell receptor beta locus. Proc Natl Acad Sci U S A. 2004;101:15712-7 pubmed
    ..These data identify Ets-1 as a critical transcription factor for pre-TCR functioning and for allelic exclusion at the TCRbeta locus. ..
  6. Eyquem S, Chemin K, Fasseu M, Chopin M, Sigaux F, Cumano A, et al. The development of early and mature B cells is impaired in mice deficient for the Ets-1 transcription factor. Eur J Immunol. 2004;34:3187-96 pubmed
    ..These findings demonstrate that the effect of Ets-1 inactivation is not restricted to the terminal B cell differentiation stage, but also affects the development and function of earlier B cell subsets. ..
  7. Zhan Y, Brown C, Maynard E, Anshelevich A, Ni W, Ho I, et al. Ets-1 is a critical regulator of Ang II-mediated vascular inflammation and remodeling. J Clin Invest. 2005;115:2508-16 pubmed
    ..Arterial wall thickening, perivascular fibrosis, and cardiac hypertrophy are significantly diminished in Ets1-/- mice compared with control mice in response to Ang II...
  8. Gerhauser I, Alldinger S, Baumgartner W. Ets-1 represents a pivotal transcription factor for viral clearance, inflammation, and demyelination in a mouse model of multiple sclerosis. J Neuroimmunol. 2007;188:86-94 pubmed
    ..Though strong Ets-1 expression in resident glial cells such as astrocytes might inhibit lesion development, delayed Ets-1 activation in inflammatory cells seemed to promote demyelination in the late phase of TME in SJL/J mice. ..
  9. Muthusamy N, Barton K, Leiden J. Defective activation and survival of T cells lacking the Ets-1 transcription factor. Nature. 1995;377:639-42 pubmed
    ..These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells. ..
  10. Ji Z, Degerny C, Vintonenko N, Deheuninck J, Foveau B, Leroy C, et al. Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation. Oncogene. 2007;26:395-406 pubmed
    ..These data show that Ets-1 can be modified by sumoylation and/or ubiquitinylation, with sumoylation repressing transcriptional activity of Ets-1 and having no clear antagonistic action on the ubiquitin-proteasome degradation pathway. ..
  11. Kim W, Sieweke M, Ogawa E, Wee H, Englmeier U, Graf T, et al. Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains. EMBO J. 1999;18:1609-20 pubmed
    ..The mutual activation of DNA binding of Ets and AML1 through the intermolecular interaction of autoinhibitory domains may represent a novel principle for the regulation of transcription factor function. ..
  12. Wai P, Mi Z, Gao C, Guo H, Marroquin C, Kuo P. Ets-1 and runx2 regulate transcription of a metastatic gene, osteopontin, in murine colorectal cancer cells. J Biol Chem. 2006;281:18973-82 pubmed
    ..Ets-1 and Runx2 are critical transcriptional regulators of OPN expression in CT26 colorectal cancer cells. Suppression of these transcription factors results in significant down-regulation of the OPN metastasis protein. ..
  13. Walunas T, Wang B, Wang C, Leiden J. Cutting edge: the Ets1 transcription factor is required for the development of NK T cells in mice. J Immunol. 2000;164:2857-60 pubmed
    b>Ets1-deficient mice develop B and T cells but display a severe defect in the development of the NK cell lineage. In this report, we demonstrate that Ets1 is also required for the development of NK1.1+ T (NK T) cells...
  14. Maroulakou I, Papas T, Green J. Differential expression of ets-1 and ets-2 proto-oncogenes during murine embryogenesis. Oncogene. 1994;9:1551-65 pubmed
  15. Ni W, Zhan Y, He H, Maynard E, Balschi J, Oettgen P. Ets-1 is a critical transcriptional regulator of reactive oxygen species and p47(phox) gene expression in response to angiotensin II. Circ Res. 2007;101:985-94 pubmed
    ..In summary, Ets-1 functions as a critical downstream transcriptional mediator of Ang II ROS generation by regulating the expression of NAD(P)H oxidase subunits such as p47(phox). ..
  16. Grenningloh R, Miaw S, Moisan J, Graves B, Ho I. Role of Ets-1 phosphorylation in the effector function of Th cells. Eur J Immunol. 2008;38:1700-5 pubmed publisher
    ..We further demonstrate that the effect of Ets-1 phosphorylation is very modest and that full-length Ets-1 and its splice variant are functionally interchangeable in the regulation of cytokine production in Th cells. ..
  17. Stamatovic S, Keep R, Mostarica Stojkovic M, Andjelkovic A. CCL2 regulates angiogenesis via activation of Ets-1 transcription factor. J Immunol. 2006;177:2651-61 pubmed
    ..Based on these findings, we suggest that Ets-1 transcription factor plays a critical role in CCL2 actions on brain endothelial cells and CCL2-induced angiogenesis. ..
  18. Xu D, Wilson T, Chan D, De Luca E, Zhou J, Hertzog P, et al. Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells. EMBO J. 2002;21:4081-93 pubmed
    ..We show that mouse ES cells lacking Ets1 are deficient in their ability to undergo UV-induced apoptosis, similar to p53 null ES cells...
  19. Foulds C, Nelson M, Blaszczak A, Graves B. Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment. Mol Cell Biol. 2004;24:10954-64 pubmed
    ..In addition, our findings decipher the mechanistic link between Ras/MAPK signaling and two specific transcription factors that are relevant to both normal development and tumorigenesis. ..
  20. Roussel M, Davis J, Cleveland J, Ghysdael J, Hiebert S. Dual control of myc expression through a single DNA binding site targeted by ets family proteins and E2F-1. Oncogene. 1994;9:405-15 pubmed
    ..Thus, E2F-1 and ets family members may independently regulate c-myc transcription through the same binding site at different times following growth factor stimulation. ..
  21. Bories J, Willerford D, Grevin D, Davidson L, Camus A, Martin P, et al. Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene. Nature. 1995;377:635-8 pubmed
    ..In contrast, Ets-1-deficient B cells were present in normal numbers but a large proportion were IgM plasma cells. Our data demonstrate that Ets-1 is essential for maintenance of the normal pool of resting T- and B-lineage cells. ..
  22. Nye J, Petersen J, Gunther C, Jonsen M, Graves B. Interaction of murine ets-1 with GGA-binding sites establishes the ETS domain as a new DNA-binding motif. Genes Dev. 1992;6:975-90 pubmed
    ..Compared to other well-characterized classes of DNA-binding proteins, Ets-1 produces a unique pattern of DNA contacts. These studies demonstrate that the ETS domain proteins bind DNA in a novel manner. ..
  23. Pufall M, Lee G, Nelson M, Kang H, Velyvis A, Kay L, et al. Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region. Science. 2005;309:142-5 pubmed
    ..Variable phosphorylation thus serves as a "rheostat" for cell signaling to fine-tune transcription at the level of DNA binding. ..
  24. Lionneton F, Lelievre E, Baillat D, Stehelin D, Soncin F. Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets-1 transcription factor. Oncogene. 2003;22:9156-64 pubmed
    ..Altogether, our data suggest that p42Ets-1 acts as a distinct transcription factor from p51Ets-1. ..
  25. Hadri L, Ozog A, Soncin F, Lompre A. Basal transcription of the mouse sarco(endo)plasmic reticulum Ca2+-ATPase type 3 gene in endothelial cells is controlled by Ets-1 and Sp1. J Biol Chem. 2002;277:36471-8 pubmed
    ..Finally, overexpression of Ets-1 induced the expression of SERCA3 in endothelial cells and in fibroblasts. ..
  26. Nakatsu F, Kadohira T, Gilbert D, Jenkins N, Kakuta H, Copeland N, et al. Genomic structure and chromosome mapping of the genes encoding clathrin-associated adaptor medium chains mu1A (Ap1m1) and mu1B (Ap1m2). Cytogenet Cell Genet. 1999;87:53-8 pubmed
    ..We also mapped AP1M2 to human chromosome 19p13.2 and Ap1m2 to the proximal region of mouse chromosome 9. The results are consistent with the fact that these regions are syntenic. ..
  27. Saldana Caboverde A, Perera E, Watkins Chow D, Hansen N, Vemulapalli M, Mullikin J, et al. The transcription factors Ets1 and Sox10 interact during murine melanocyte development. Dev Biol. 2015;407:300-12 pubmed publisher
    ..We identified a G-to-A nucleotide transition in exon 3 of the Ets1 gene in variable spotting, which results in a missense G102E mutation...
  28. Das L, Vinayak M. Long-term effect of curcumin down-regulates expression of tumor necrosis factor-? and interleukin-6 via modulation of E26 transformation-specific protein and nuclear factor-?B transcription factors in livers of lymphoma bearing mice. Leuk Lymphoma. 2014;55:2627-36 pubmed publisher
  29. Furlan A, Vercamer C, Bouali F, Damour I, Chotteau Lelievre A, Wernert N, et al. Ets-1 controls breast cancer cell balance between invasion and growth. Int J Cancer. 2014;135:2317-28 pubmed publisher
    ..This work also demonstrates that 3D models may reveal mechanisms of tumor biology that are cryptic in standard 2D models. ..
  30. Grevin D, Chen J, Raes M, Stehelin D, Vandenbunder B, Desbiens X. Involvement of the proto-oncogene c-ets 1 and the urokinase plasminogen activator during mouse implantation and placentation. Int J Dev Biol. 1993;37:519-29 pubmed
    Many of the Ets proteins have been shown to be transcription activators. In vitro, Ets 1 proteins are involved in the transcriptional induction of genes such as stromelysin 1, collagenase 1 or urokinase type plasminogen activator, which ..
  31. Kumar P, Pandey K. Cooperative activation of Npr1 gene transcription and expression by interaction of Ets-1 and p300. Hypertension. 2009;54:172-8 pubmed publisher
    ..The present findings should yield important insights into the molecular signaling governing Npr1 gene transcription, an important regulator in the control of hypertension and cardiovascular events. ..
  32. Ben David Y, Giddens E, Letwin K, Bernstein A. Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. Genes Dev. 1991;5:908-18 pubmed
    ..The involvement of the murine Fli-1, Spi-1, and avian v-ets genes in erythroleukemia induction suggests that activation of ets gene family members plays an important role in the progression of these multistage malignancies...
  33. Lee C, Kwon H, Sahoo A, Hwang W, So J, Hwang J, et al. Interaction of Ets-1 with HDAC1 represses IL-10 expression in Th1 cells. J Immunol. 2012;188:2244-53 pubmed publisher
    ..Coexpression of Ets-1 with HDAC1 synergistically repressed IL-10 transcription activity. In summary, our data suggest that an interaction of Ets-1 with HDAC1 represses the Il10 gene expression in Th1 cells. ..
  34. Cauchy P, Maqbool M, Zacarias Cabeza J, Vanhille L, Koch F, Fenouil R, et al. Dynamic recruitment of Ets1 to both nucleosome-occupied and -depleted enhancer regions mediates a transcriptional program switch during early T-cell differentiation. Nucleic Acids Res. 2016;44:3567-85 pubmed publisher
    b>Ets1 is a sequence-specific transcription factor that plays an important role during hematopoiesis, and is essential for the transition of CD4(-)/CD8(-) double negative (DN) to CD4(+)/CD8(+) double positive (DP) thymocytes...
  35. Lee S, Schorey J. Activation and mitogen-activated protein kinase regulation of transcription factors Ets and NF-kappaB in Mycobacterium-infected macrophages and role of these factors in tumor necrosis factor alpha and nitric oxide synthase 2 promoter function. Infect Immun. 2005;73:6499-507 pubmed
    ..smegmatis-infected macrophages are responsible, at least in part, for the increased TNF-alpha and NOS2 production observed in these infected cells and that ERK1/2 is required for Ets/Elk activity and full TNF-alpha production. ..
  36. Tsao H, Tai T, Tseng W, Chang H, Grenningloh R, Miaw S, et al. Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL-2 promoter. Proc Natl Acad Sci U S A. 2013;110:15776-81 pubmed publisher
    ..Thus, Ets-1 promotes the expression of IL-2 by modulating the activity of NFAT. ..
  37. Mouly E, Chemin K, Nguyen H, Chopin M, Mesnard L, Leite de Moraes M, et al. The Ets-1 transcription factor controls the development and function of natural regulatory T cells. J Exp Med. 2010;207:2113-25 pubmed publisher
    ..These data demonstrate that Ets-1 is required for the development of natural T reg cells and suggest a role for this transcription factor in the regulation of Foxp3 expression. ..
  38. Ramirez K, Chandler K, Spaulding C, Zandi S, Sigvardsson M, Graves B, et al. Gene deregulation and chronic activation in natural killer cells deficient in the transcription factor ETS1. Immunity. 2012;36:921-32 pubmed publisher
    ..and genome-wide binding analyses combined with developmental and functional studies to unveil three roles for the ETS1 transcription factor in NK cells...
  39. Watanabe D, Takagi H, Suzuma K, Suzuma I, Oh H, Ohashi H, et al. Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization. Am J Pathol. 2004;164:1827-35 pubmed
    ..Ets-1 up-regulation is involved in the development of retinal neovascularization, and inhibition of Ets-1 may be beneficial in the treatment of ischemic ocular diseases. ..
  40. Strempel J, Grenningloh R, Ho I, Vercelli D. Phylogenetic and functional analysis identifies Ets-1 as a novel regulator of the Th2 cytokine gene locus. J Immunol. 2010;184:1309-16 pubmed publisher
    ..Collectively, these data suggest that Ets-1 contributes to Th2 cytokine gene regulation by interacting with multiple cis-regulatory regions throughout the Th2 locus. ..
  41. Polansky J, Schreiber L, Thelemann C, Ludwig L, Krüger M, Baumgrass R, et al. Methylation matters: binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells. J Mol Med (Berl). 2010;88:1029-40 pubmed publisher
    ..We therefore propose that Ets-1 is part of a larger protein complex, which binds to the TSDR only in its demethylated state, thereby restricting stable Foxp3 expression to the Treg lineage. ..
  42. John S, Clements J, Russell L, Garrett Sinha L. Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1. J Biol Chem. 2008;283:951-62 pubmed
    ..These results reveal a previously unknown mechanism for the control of Blimp-1 activity by Ets-1 and suggest that expression of Ets-1 must be down-regulated before plasmacytic differentiation can occur. ..
  43. Li L, Miao X, Ni R, Miao X, Wang L, Gu X, et al. Epithelial-specific ETS-1 (ESE1/ELF3) regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation. Immunol Res. 2015;62:198-212 pubmed publisher
    ..Taken together, our data suggested that ESE1/ELF3 may promote the UC progression via accelerating NF-κB activation and thus facilitating IEC apoptosis. ..
  44. Tang J, Carmichael C, Shi W, Metcalf D, Ng A, Hyland C, et al. Transposon mutagenesis reveals cooperation of ETS family transcription factors with signaling pathways in erythro-megakaryocytic leukemia. Proc Natl Acad Sci U S A. 2013;110:6091-6 pubmed publisher
    ..The genes encoding the E-twenty-six (ETS) transcription factors Ets related gene (Erg) and Ets1 were the most common sites for transposon insertion in SB-induced JAK2V617F-positive erythroleukemias, present in ..
  45. Subrata L, Voon D, Yeoh G, Ulgiati D, Quail E, Abraham L. TNF-inducible expression of lymphotoxin-? in hepatic cells: an essential role for NF-?B and Ets1 transcription factors. Cytokine. 2012;60:498-504 pubmed publisher
    ..Here we show that TNF is able to upregulate LT-? expression in hepatic cells at the transcriptional level by the binding of NF-?B p50/p65 heterodimers and Ets1 to their respective sites in the LT-? promoter.
  46. Hume D, Yue X, Ross I, Favot P, Lichanska A, Ostrowski M. Regulation of CSF-1 receptor expression. Mol Reprod Dev. 1997;46:46-52; discussion 52-3 pubmed
  47. Ernst P, Hahm K, Smale S. Both LyF-1 and an Ets protein interact with a critical promoter element in the murine terminal transferase gene. Mol Cell Biol. 1993;13:2982-92 pubmed
    ..The role of LyF-1 is less clear; it might act in conjunction with the Ets protein bound at the D' element or it might be unnecessary for D' activity. ..
  48. Klocke R, Augustin A, Ronsiek M, Stief A, van Der Putten H, Jockusch H. Dynamin genes Dnm1 and Dnm2 are located on proximal mouse chromosomes 2 and 9, respectively. Genomics. 1997;41:290-2 pubmed
    ..Potential relations of both loci to disease genes are discussed. ..
  49. Feng W, Chumley P, Hua P, Rezonzew G, Jaimes D, Duckworth M, et al. Role of the transcription factor erythroblastosis virus E26 oncogen homolog-1 (ETS-1) as mediator of the renal proinflammatory and profibrotic effects of angiotensin II. Hypertension. 2012;60:1226-33 pubmed publisher
  50. Sugiura K, Ito K. Roles of Ets-1 and p70S6 kinase in chondrogenic and gliogenic specification of mouse mesencephalic neural crest cells. Mech Dev. 2010;127:169-82 pubmed publisher
    ..These results suggest that Ets-1 activated by the Erk pathway promotes chondrogenic specification and p70S6k activated by both the Erk and Akt pathways plays an important role in gliogenic specification. ..
  51. Szpirer C, Molné M, Antonacci R, Jenkins N, Finelli P, Szpirer J, et al. The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat. Proc Natl Acad Sci U S A. 1994;91:11849-53 pubmed
    ..Our data extend the conserved synteny established between certain human, mouse, and rat Chrs. ..
  52. Zamisch M, Tian L, Grenningloh R, Xiong Y, Wildt K, Ehlers M, et al. The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus. J Exp Med. 2009;206:2685-99 pubmed publisher
    The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood...
  53. Baillat D, Laitem C, Leprivier G, Margerin C, Aumercier M. Ets-1 binds cooperatively to the palindromic Ets-binding sites in the p53 promoter. Biochem Biophys Res Commun. 2009;378:213-7 pubmed publisher
    ..Thus, the cooperative binding model that we initially proposed for the stromelysin-1 promoter may be a general mechanism of Ets-1 binding to palindromic EBS separated by 4bp and a way to counteract binding site degeneracy. ..