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:

DNA binding of USF is required for specific E-box dependent gene activation in vivo

Oncogene volume 18, pages 7200–7211 (1999)Cite this article

Abstract

Although USF-1 and -2 are the major proteins that bind to Myc-regulated E-box (CACGTG) elements in many cells, there is no clear role for USF during Myc-dependent gene regulation. Using dominant negative alleles of USF-1 we now show that DNA binding by USF at a Myc-regulated E-box limits the ability of another E-box binding factor, TFE-3, to activate a target gene of Myc in vivo and to stimulate S phase entry in resting fibroblasts. Similarly, dominant negative alleles of USF-1 relieve the restriction that prevents activation of the IgH enhancer by TFE-3 in non B-cells. DNA binding activity of USF complexes is abundant in primary human B-cells and is significantly downregulated during B-cell immortalization. Re-expression of USF-1 in immortalized B-cells retards proliferation. Our data establish an essential role for USF in restricting E-box dependent gene activation in vivo and suggest that this control is relaxed during cellular immortalization.

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
Figure 8
Figure 9

Similar content being viewed by others

References

  • Alland L, Muhle R, Hou H, Potes J, Chin L, Schreiber-Agus N and dePinho R. . 1997 Nature 387: 49–55.

  • Aperlo C, Boulukos KE and Pognonec P. . 1996 Eur. J. Biochem. 241: 249–253.

  • Beckmann H, Su LK and Kadesch T. . 1990 Genes Dev. 4: 167–179.

  • Bello-Fernandez C, Packham G and Cleveland JL. . 1993 Proc. Natl. Acad. Sci. USA 90: 7804–7808.

  • Ben-Bassat H, Goldblum N, Mitrani S, Goldblum T, Yoffey JM, Cohen MM, Bentwich Z, Ramot B, Klein E and Klein G. . 1977 Int. J. Cancer 19: 27–33.

  • Berger A, Cultaro CM, Segal S and Spiegel S. . 1998 Biochim. Biophys. Acta 1390: 225–236.

  • Bouchard C, Staller P and Eilers M. . 1998 Trends Cell Biol. 1998: 8: 202–206.

  • Boyd KE, Wells J, Gutman J, Bartley SM and Farnham PJ. . 1998 Proc. Natl. Acad. Sci. USA 95: 13887–13892.

  • Carter RS, Ordentlich P and Kadesch T. . 1997 Mol. Cell. Biol. 17: 18–23.

  • Desbarats L, Gaubatz S and Eilers M. . 1996 Genes Dev. 10: 447–460.

  • Ferré D'Amaré AR, Prendergast GC, Ziff EB and Burley SK. . 1993 Nature 363: 38–45.

  • Ferré D'Amaré AR, Pognonec P, Roeder RG and Burley SK. . 1994 EMBO J. 13: 180–189.

  • Fisher DE, Carr CS, Parent LA and Sharp PA. . 1991 Genes Dev. 5: 2342–2352.

  • Galibert MD, Boucontet L, Goding CR and Meo T. . 1997 J. Immunol. 159: 6176–6183.

  • Gaubatz S, Imhof A, Dosch R, Werner O, Mitchell P, Buettner R and Eilers M. . 1995 EMBO J. 14: 1508–1529.

  • Grandori C and Eisenman RN. . 1997 Trends Biochem. Sci. 22: 177–181.

  • Genetta T, Ruezinsky D and Kadesch T. . 1994 Mol. Cell. Biol. 14: 6153–6163.

  • Harper SE, Qiu Y and Sharp PA. . 1996 Proc. Natl. Acad. Sci. USA 93: 8536–8540.

  • Henriksson M and Lüscher B. . 1996 Cancer Research 68: 109–182.

  • Laherty CD, Yang WM, Sun JM, Davie JR, Seto E and Eisenman RN. . 1997 Cell 89: 349–356.

  • Luo X and Sawadogo M. . 1996 Proc. Natl. Acad. Sci. USA 93: 1308–1313.

  • Maekawa T, Sudo T, Kurimoto M and Ishii S. . 1991 Nucleic Acids Res. 19: 4689–4694.

  • Merrell K, Wells S, Henderson A, Gorman J, Alt F, Stall A and Calame K. . 1997 Mol. Cell. Biol. 17: 3335–3344.

  • Moriizumi S, Gourdon L, Lefrancois-Martinez AM, Kahn A and Raymondjean M. . 1998 Gene Expr. 7: 103–113.

  • Muhlethaler-Mottet A, Di Berardino W, Otten LA and Mach B. . 1998 Immunity 8: 157–166.

  • Peukert K, Staller P, Schneider A, Carmichael G, Hänel F and Eilers M. . 1997 EMBO J. 16: 5672–5686.

  • Sieweke MH, Tekotte H, Jarosch U and Graf T. . 1998 EMBO J. 17: 1728–1739.

  • Sinclair A and Farrell PJ. . 1995 In: Methods in Molecular Genetics. Adolf KW (Ed).. Academic Press: Orlando, FL pp.89–100.

    Google Scholar 

  • Sirito M, Lin Q, Deng JM, Behringer RR and Sawadogo M. . 1998 Proc. Natl. Acad. Sci. USA 95: 3758–3763.

  • Sommer A, Hilfenhaus S, Menkel A, Kremmer E, Seiser C, Loidl P and Lüscher B. . 1997 Curr. Biol. 7: 357–365.

  • Tobias KE, Shor J and Kahana C. . 1995 Oncogene 11: 1721–1727.

  • Tsuneoka M, Nakano F, Ohgusu H and Mekada E. . 1997 Oncogene 14: 2301–2311.

  • Viollet B, Lefrancois-Martinez AM, Henrion A, Kahn A, Raymondjean M and Martinez A. . 1996 J. Biol. Chem. 271: 1405–1415.

  • Xiao Q, Claassen G, Shi J, Adachi S, Sedivy J and Hann SR. . 1998 Genes & Dev. 12: 3803–3808.

Download references

Acknowledgements

We would like to thank M Brimmell for technical assistance and Dr J Cleveland for reviewing the manuscript. We also thank Dr M Sawadogo for anti-USF antiserum, Dr A Kahn for IgGM, IgGG and IgGO anti-USF antisera, Dr R Eisenman for the kind gift of anti-Mnt antiserum, Dr M Pagano for anti-cyclin A antiserum, and Dr T Kadesch for IgH reporter plasmids. We would like to thank B Lüscher and C Czerni for transformation assays. This work was supported by the Ludwig Institute for Cancer Research, by the Human Frontiers of Science Organisation, and by the Deutsche Forschungsgemeinschaft via SFB229 and SFB379.

Author information

Authors and Affiliations

  1. Institute for Molecular Biology and Tumour Research, University of Marburg, Emil-Mannkopff-Str 2, 35033, Marburg, Germany

    Astrid Kiermaier, Laurie Desbarats & Martin Eilers

  2. Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London, W2 1PG, UK

    Jonathan M Gawn, Paul J Farrell & Graham Packham

  3. Biochemical Instrumentation Programme, EMBL, Meyerhofstr 1, 69117, Heidelberg, Germany

    Rainer Saffrich & Wilhelm Ansorge

  4. Department of Medical Microbiology, Virology and Cell Biology, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London, W2 1PG, UK

    Paul J Farrell & Graham Packham

Authors
  1. Astrid Kiermaier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan M Gawn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laurie Desbarats
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rainer Saffrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wilhelm Ansorge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul J Farrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martin Eilers
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Graham Packham
    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

Kiermaier, A., Gawn, J., Desbarats, L. et al. DNA binding of USF is required for specific E-box dependent gene activation in vivo. Oncogene 18, 7200–7211 (1999). https://doi.org/10.1038/sj.onc.1203166

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203166

Keywords

This article is cited by

Search

Advanced search

Quick links