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Ets transcription factors cooperate with Sp1 to activate the human Tenascin-C promoter

Oncogene volume 18, pages 7755–7764 (1999)Cite this article

Abstract

Tenascin-C (TN-C), an extracellular matrix glycoprotein is expressed during embryonic development, but is present only at low levels in normal adult tissues. TN-C is re-expressed during wound healing, fibrotic diseases and in cancer. To better understand the mechanisms that control TN-C gene expression, we examined the regulation of the human TN-C promoter in human fibroblasts. We demonstrate that a short segment of the TN-C promoter between bp −133 and −27 contains three evolutionarily conserved Ets binding sites (EBS). These three EBSs bind in vitro expressed Fli1 protein and mediate transactivation of the TN-C gene by Fli1. Furthermore, two proximal EBSs contribute significantly to basal activity of the TN-C promoter. GABP, which is present in human fibroblast nuclear extracts, interacts with the two proximal EBSs. In addition, several Sp1 and Sp3 binding sites have been located in close proximity to the EBSs within this promoter region. The studies performed in Drosophila cells demonstrate that either Fli1 or GABPα+β1 functionally interact with Sp1 resulting in a synergistic stimulation of the TN-C promoter activity. In conclusion, this study shows for the first time that the TN-C gene is regulated by Ets proteins, which together with Sp1 act as potent activators of TN-C expression.

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Acknowledgements

We thank Dr R Gherzi for providing pTN-I-CAT construct and Dr SL McKnight for providing GABPα and β1 cDNAs and antibodies. We also thank Dr T Hsu for critically reading the manuscript and many helpful suggestions. This work was supported by National Institutes of Health grant AR42334 and by RGK Foundation.

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Author notes

  1. Fumiaki Shirasaki and Huda A Makhluf: The first two authors contributed equally to this paper

Authors and Affiliations

  1. Department of Medicine, Division of Rheumatology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, 29425-2229, South Carolina, SC, USA

    Fumiaki Shirasaki, Huda A Makhluf & Maria Trojanowska

  2. Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, 29425-2229, South Carolina, SC, USA

    Carwile LeRoy

  3. Center for Molecular and Structural Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, 29425-2229, South Carolina, SC, USA

    Dennis K Watson

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  1. Fumiaki Shirasaki
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Shirasaki, F., Makhluf, H., LeRoy, C. et al. Ets transcription factors cooperate with Sp1 to activate the human Tenascin-C promoter. Oncogene 18, 7755–7764 (1999). https://doi.org/10.1038/sj.onc.1203360

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