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FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain

Oncogene volume 22, pages 3319–3329 (2003)Cite this article

Abstract

Although most Ets transcription factors have been characterized as transcriptional activators, some of them display repressor activity. Here we characterize an Ets-family member, the very specifically expressed human Fifth Ewing Variant (FEV), as a transcriptional repressor. We show that among a broad range of human cell lines, only Dami megakaryocytic cells express FEV. This nuclear protein binds to Ets-binding sites, such as that of the human ICAM-1 promoter. We used this promoter to demonstrate that FEV can repress both basal transcription and, even more strongly, ectopically Ets-activated transcription. We identified two domains responsible for FEV-mediated repression: the ETS domain, responsible for passive repression, and the carboxy-terminal alanine-rich domain, involved in active repression. In the Ets-independent LEXA system also, FEV acts as a transcriptional repressor via its alanine-rich carboxy-terminal domain. The mechanism by which FEV actively represses transcription is currently unknown, since FEV-triggered repression is not reversed by the histone deacetylase inhibitor trichostatin A. We also showed that long-term overexpression of FEV proteins containing the alanine-rich domain prevents cell clones from growing, whereas clones expressing a truncated FEV protein lacking this domain develop like control cells. This confirms the importance of this domain in FEV-triggered repression.

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Acknowledgements

PM and FT should be considered to be the first authors. This paper is dedicated to the late Rudy Deschuyteneer. We thank to Pascale Putmans for her excellent technical assistance. PM and CB are recipients of a ‘Télévie’ grant (FNRS, Belgium). FT is a recipient of an FRIA grant (FNRS, Belgium). This work was carried out, thanks to grants awarded by the ‘Centre National de la Recherche Scientifique. (France), the ‘Institut Pasteur de Lille’, the ‘Association pour la Recherche contre le Cancer’ (France), the ‘Ligue Régionale Contre le Cancer’ (Comité Nord, France), the ‘Fonds National de la Recherche Scientifique’ (FNRS, Belgium), and the ‘Action de Recherche Concertée (Communauté Françhise de Belgique)’ (Belgium).

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  1. Laboratoire de Virologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, CP 614, 808 route de Lennik, Brussels, 1070, Belgium

    Philippe Maurer, France T'Sas, Nathalie Callens, Carmen Brenner & Yvan de Launoit

  2. UMR 8117 CNRS, Institut Pasteur de Lille, Université de Lille I, Institut de Biologie de Lille, BP 447, 1 rue Calmette, Lille Cedex, 59021, France

    Laurent Coutte, Nathalie Callens, Yvan de Launoit & Jean-Luc Baert

  3. Département de Biologie Moléculaire, Laboratoire de Chimie Biologique, Institut de Biologie et de Médecine Moléculaires, Faculté des Sciences, Université Libre de Bruxelles, Rue des Professeurs Jeener et Brachet 12, Gosselies, 6041, Belgium

    Carine Van Lint

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  1. Philippe Maurer
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Correspondence to Yvan de Launoit.

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Maurer, P., T'Sas, F., Coutte, L. et al. FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain. Oncogene 22, 3319–3329 (2003). https://doi.org/10.1038/sj.onc.1206572

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