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  • Original Paper
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Mutual repression of transcriptional activation between the ETS-related factor ERG and estrogen receptor

Oncogene volume 22, pages 8072–8084 (2003)Cite this article

Abstract

Transcription factors are known to interact with each other to modulate their transcriptional activity. In this study, we found that the transcriptional activity of human Erg (one of the Ets family-transcription factors) was repressed by several nuclear receptors, including human estrogen receptor ERα, nonsteroid receptors and orphan receptors. Conversely, Erg inhibited ERα-dependent transcription. These reciprocal functional interactions extended to other nuclear receptors such as thyroid hormone and retinoic acid receptors, as well as to Fli1, an ERG-related ETS factor. Although similarly inhibited by overexpression of the orphan nuclear receptors ERR1 and RORα, ERG activity was unaffected by either REV-ERBα1 or COUP-TFII. The antagonism between ERG and ERα did not depend on DNA binding inhibition or direct protein–protein interactions. Repression of ERα-dependent transcription required the carboxyterminal and aminoterminal transactivation domains of Erg whereas the carboxyterminal AF-2 domain of ERα was necessary for repression of Erg activity. Reciprocal inhibition between Erg and ERα was not alleviated by overexpressing CBP, SRC-1 or RIP 140, three nuclear coactivator proteins. A negative cross-talk observed between Erg and ERα expands their potential range of regulation and may be relevant in vivo, particularly in endothelial, urogenital and cartilaginous tissues where both factors are expressed.

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Acknowledgements

We are indebted to Drs V Cavailles, D Monté and D McDonnel for the kind gift of SRC-1 and RIP140 expression plasmids, CBP expression plasmid and VP16-nuclear receptor fusion constructs, respectively. We also thank Drs J Coll and P Guillem for critical reading of the manuscript, and Dr JL Wemeau for constant encouragement. This work was supported by grants from CNRS, Institut Pasteur de Lille, Université de Lille II and Association pour la Recherche sur le Cancer.

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  1. Alexis Verger

    Present address: Department Biochemistry, G08, University of Sydney, NSW, 2006, Australia

Authors and Affiliations

  1. CNRS UMR 8526, Institut de Biologie de Lille, France

    Virginie Vlaeminck-Guillem, Alexis Verger, Nathalie Tomavo, Dominique Stehelin & Martine Duterque-Coquillaud

  2. CNRS UMR 5665, Ecole Normale Supérieure de Lyon, France

    Jean-Marc Vanacker & Vincent Laudet

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  1. Virginie Vlaeminck-Guillem
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Correspondence to Martine Duterque-Coquillaud.

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Vlaeminck-Guillem, V., Vanacker, JM., Verger, A. et al. Mutual repression of transcriptional activation between the ETS-related factor ERG and estrogen receptor. Oncogene 22, 8072–8084 (2003). https://doi.org/10.1038/sj.onc.1207094

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