Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

The GATA-1 and Spi-1 transcriptional factors bind to a GATA/EBS dual element in the Fli-1 exon 1

Oncogene volume 18, pages 5535–5545 (1999)Cite this article

Abstract

Fli-1 is a proto-oncogene which is rearranged in tumors induced by three different retroviruses, Cas-Br-E, F-MuLV, and 10A1. This gene is a member of the Ets gene family, a class of transcription factors that recognize and bind to a DNA motif known as the Ets binding site (EBS). Our laboratory has previously cloned and characterized the promoter region of both human and mouse Fli-1 genes. We had then identified several regulatory elements conserved between the two species. Two of them, an exon 1 GATA/EBS dual element and an EBS element located in the 5′ end of intron 1, were analysed in the present study. EMSA analysis performed with nuclear extracts from different cell lines showed that the EBS element in intron 1 (EBSi) was bound by one potential Ets-related ubiquitous factor. The GATA/EBS element was bound by several factors that seemed Ets-related, one of which was found to be specifically expressed in hematopoietic cells. the GATA/EBS dual element was thus chosen for further analysis. A human Fli-1-derived genomic fragment containing the GATA/EBS led to enhanced transcription when positioned upstream of the SV40 promoter in the erythroleukemic HEL cell line. In addition, an increasing number of GATA/EBS oligonucleotides upstream of this same promoter resulted in a copy number-dependent increase in luciferase activity which was greatly reduced when the EBS consensus sequence was mutated. One of the factors binding to the GATA/EBS region was identified to be Spi-1 by supershift analysis and was also shown to bind to the EBS element of the human Ets-2 gene. Supershift analysis also demonstrated the binding of the GATA-1 factor to the GATA/EBS dual element. Our results suggest that Spi-1 and GATA-1 might play a key role in the regulation of Fli-1.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Aumont FL, Trudel P and Wall L. . 1993 Differentiation 52: 169–176.

  • Barbeau B, Bergeron D, Beaulieu M, Nadjem Z and Rassart E. . 1996 Biochim. Biophys. Acta 1307: 220–232.

  • Ben-David Y, Giddens EB and Bernstein A. . 1990 Proc. Natl. Acad. Sci. USA 87: 1332–1336.

  • Ben-David Y, Giddens EB, Letwin K and Bernstein A. . 1991 Genes Dev. 5: 908–918.

  • Bergeron D, Poliquin L, Kozak CA and Rassart E. . 1991 J. Virol. 65: 7–15.

  • Bergeron D, Poliquin L, Houde J, Barbeau B and Rassart E. . 1992 Virology 191: 661–669.

  • Bergeron D, Houde J, Poliquin L, Barbeau B and Rassart E. . 1993 Leukemia 7: 954–962.

  • Bhat NK, Fisher RJ, Fujiwara, Ascione R and Papas TS. . 1987 Proc. Natl. Acad. Sci. USA 84: 3161–3165.

  • Bhattacharya G, Lee L, Reddy SP and Rao VN. . 1993 Oncogene 8: 3459–3464.

  • Bories J-C, Willerford DM, Grévin D, Davidson L, Camus A, Martin P, Stéhélin D and Alt FW. . 1995 Nature 377: 635–638.

  • Brown TA and McKnight SL. . 1992 Gene Dev. 6: 2500–2512.

  • Carvalho M and Derse D. . 1993a J. Virol. 67: 3885–3890.

  • Carvalho M and Derse D. . 1993b Ninth Annual Meeting on Oncogenes, Frederick, Maryland p.224. (Abstract).

  • Chen JS and Wright CD. . 1993 Oncogene 8: 3375–3383.

  • Chen H-M, Ray-Gallet D, Zhang P, Hetherington CJ, Gonzalez DA, Zhang D-E, Moreau-Gachelin F and Tenen DG. . 1995 Oncogene 11: 1549–1560.

  • Chomsinsky P and Sacchi N. . 1987 Anal. Biochem. 162: 156–159.

  • Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert H, de Jong P, Rouleau G, Aurias A and Thomas G. . 1992 Nature 359: 162–165.

  • Eichbaum QG, Iyer R, Raveh DP, Mathieu C and Ezekowitz RAB. . 1994 J. Exp. Med. 179: 1985–1996.

  • Feinman R, Qiu WQ, Pearse RN, Nikolajczyk BS, Sen R, Sheffery M and Ravetch JV. . 1994 EMBO J. 13: 3852–3860.

  • Galson DL, Hensold JO, Bishop TR, Schalling M, D'Andrea AD, Jones C, Auron PE and Houseman DE. . 1993 Mol. Cell. Biol. 13: 2929–2941.

  • Gauthier JM, Bourachot B, Doucas V, Yamir M and Moreau-Gachelin F. . 1993 EMBO J. 12: 5089–5096.

  • Goebl MG, Moreau-Gachelin F, Ray P, Tambourin P, Tavitan A, Klemsz MJ, McKercher SR, Celada A, Van Bereven C and Maki RA. . 1990 Cell 61: 1165–1166.

  • Goldberg Y, Treier M, Ghysdael J and Bohmann D. . 1994 J. Biol. Chem. 269: 16566–16573.

  • Hahn SL and Wasylyk B. . 1994 Oncogene 9: 2499–2512.

  • Hall CV, Jacob PE, Rinfold GM and Lee F. . 1983 J. Mol. Appl. Genet. 2: 101–105.

  • Henkel G and Brown MA. . 1994 Proc. Natl. Acad. Sci. USA 91: 7737–7741.

  • Hromas R, May W, Denny C, Raskind W, Moore J, Maki RA, Beck E and Klemsz MJ. . 1993a Biochim. Biophys. Acta 1172: 155–158.

  • Hromas R, Orazi A, Neiman RS, Maki R, Van Bevaran C, Moore J and Klemsz M. . 1993b Blood 82: 2998–3004.

  • Jorcyk CL, Watson DK, Mavrothalassitis GJ and Papas TS. . 1991 Oncogene 6: 523–532.

  • Klemsz MJ, Raki RA, Papayannopoulou T, Moore J and Hromas R. . 1993 J. Biol. Chem. 288: 5769–5773.

  • Klemsz MJ, McKercher SR, Celada A, Van Beveren C and Maki RA. . 1990 Cell 61: 113–124.

  • LaMarco K, Thompson CC, Byers PP, Walton EM and McKnight SL. . 1991 Science 253: 789–792.

  • Majérus M-A, Bibollet-Ruche F, Telliez JB, Wasylyk B and Bailleul B. . 1992 Nucl. Acids Res. 20: 2699–2703.

  • Mavrothalassitis GJ and Papas TS. . 1991 Cell Growth Differ. 2: 215–224.

  • Mavrothalassitis GJ, Watson DK and Papas TS. . 1990 Proc. Natl. Acad. Sci. USA 87: 1047–1051.

  • May WA, Gishizky ML, Lessnick SL, Lunsford LB, Lewis BC, Delattre O, Zucman J, Thomas G and Denny CT. . 1993 Proc. Natl. Acad. Sci. USA 90: 5752–5756.

  • Mélet F, Motro B, Rossi DJ, Zhang L and Bernstein A. . 1996 Mol. Cell. Biol. 16: 2708–2718.

  • Moreau-Gachelin F. . 1994 Biochim. Biophys. Acta 1198: 149–163.

  • Moreau-Gachelin F, Tavitian A and Tambourin P. . 1988 Nature 331: 277–280.

  • Moreau-Gachelin F, Wendling F, Molina T, Denis N, Titeux M, Grimber G, Briand P, Vainchenker W and Tavitian A. . 1996 Mol. Cell. Biol. 16: 2453–2463.

  • Muthusany N, Barton K and Leiden JM. . 1995 Nature 377: 639–642.

  • Nelsen B, Tian G, Erman B, Gregoire J, Maki R, Graves B and Sen R. . 1993 Science 261: 82–86.

  • Oka T, Rairkar A and Chen JH. . 1991 Oncogene 6: 2077–2083.

  • Orkin SH. . 1992 Blood 80: 575–581.

  • Ott D, Keller J and Rein A. . 1994 Virology 205: 563–568.

  • Pongubala JMR, Nagalapalli S, Klemsz MJ, McKercher SR, Maki RA and Atchison ML. . 1992 Mol. Cell. Biol. 12: 368–372.

  • Prasad DDK, Rao VN and Reddy ESP. . 1992 Cancer Res. 52: 5833–5837.

  • Prasad DDK, Lee L, Rao VN and Reddy ESP. . 1998 Oncogene 17: 1149–1157.

  • Rao VN and Reddy SP. . 1993 Cancer Res. 53: 215–220.

  • Reddy A, Yang B-S, Yue X, Barnett CJK, Ross IL, Sweet MJ, Hume DA and Ostrowski MC. . 1994 J. Exp. Med. 180: 2309–2319.

  • Rivera RR, Stuiver MH, Steenbergen R and Murre C. . 1993 Mol. Cell. Biol. 13: 7163–7169.

  • Schneikert J, Lutz Y and Wasylyk B. . 1992 Oncogene 7: 249–256.

  • Scott EW, Simon MC, Anastasi J and Singh H. . 1994 Science 265: 1573–1577.

  • Seth A, Robinson L, Thompson DM, Watson DK and Papas TS. . 1993 Oncogene 8: 1783–1790.

  • Sgouras DN, Athanasiou MA, Beal Jr GJ, Fisher RJ, Blair DG and Mavrothalassitis GJ. . 1995 EMBO J. 14: 4781–4793.

  • Siddique HR, Rao VN, Lee L and Reddy SP. . 1993 Oncogene 8: 1751–1755.

  • Wall L, deBoer E and Grosveld F. . 1988 Genes Dev. 2: 1089–1100.

  • Wasylyk B, Hahn SL and Giovane A. . 1993 Eur. J. Biochem. 211: 7–18.

  • Watson DK, Smyth FE, Thompson DM, Cheng JQ, Testa JR, Papas TS and Seth A. . 1992 Cell Growth Differ. 3: 705–713.

  • Zhang L, Eddy A, Teng Y-T, Fritzler M, Kluppel M, Melet F and Bernstein A. . 1995 Mol. Cell. Biol. 15: 6961–6970.

  • Zhang L, Lemarchandel V, Romeo P-H, Ben-David Y, Greer P and Bernstein A. . 1993 Oncogene 8: 1621–1630.

Download references

Acknowledgements

We thank Marc Desforges for oligonucleotide synthesis; A Bernstein, F Moreau-Gachelin and L Wall for the gift of anti Fli-1, Spi-1 and GATA-1 antibodies respectively; A Friedman and A Nepveu for the gift of 32Dcl.3 and HEL cells respectively. B Barbeau was supported by a scholarship from Le Fonds pour la Formation de Chercheurs et l'Aide à la Recherche (FCAR). This work was supported by grant MT-7754 from the Medical Research Council of Canada and grant 007072 from the National Cancer Institute of Canada to E Rassart.

Author information

Author notes

  1. Benoit Barbeau and Corinne Barat: B Barbeau and C Barat contributed equally to this work

Authors and Affiliations

  1. Département des Sciences Biologiques, Laboratoire de biologie moléculaire, Université du Québec à Montréal, Montréal, Québec, Canada

    Benoit Barbeau, Corinne Barat, Dominique Bergeron & Eric Rassart

Authors
  1. Benoit Barbeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Corinne Barat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dominique Bergeron
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric Rassart
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barbeau, B., Barat, C., Bergeron, D. et al. The GATA-1 and Spi-1 transcriptional factors bind to a GATA/EBS dual element in the Fli-1 exon 1. Oncogene 18, 5535–5545 (1999). https://doi.org/10.1038/sj.onc.1202913

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202913

Keywords

This article is cited by

Search

Advanced search

Quick links