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Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets-1 transcription factor

Oncogene volume 22, pages 9156–9164 (2003)Cite this article

Abstract

We have identified the mouse exon VII splice variant of the Ets-1 transcription factor. The variant is expressed in all cell lines which express ets-1, at lower levels, it is also expressed in the mouse embryo in vivo. The corresponding protein, p42Ets-1, is a transcription factor as it is able to bind to specific DNA sequences and to transactivate a bona fide ETS reporter vector. A comparison of optimal DNA-binding sites shows that p42Ets-1 binds to more various DNA sequences than p51Ets-1; p42Ets-1 recognizes the same optimal consensus sequence as p51Ets-1, but also many variations of it, mainly at base −1, which is located just prior to the GGAA/T core sequence. The binding differences were quantified by surface plasmon resonance analyses and the protein region responsible for the differences in DNA sequence recognition located in the Val280-Glu302 fragment, which is encoded by exon VII. The specific DNA-binding properties of each isoform translates into clear differences in activity, p42Ets-1 transactivates the natural VE-cadherin gene promoter through both ETS-binding site (EBS)2 and EBS4 whereas p51Ets-1 is mainly active on EBS4. Altogether, our data suggest that p42Ets-1 acts as a distinct transcription factor from p51Ets-1.

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Abbreviations

EBS:

ETS-binding site

EMSA:

electro-mobility shift assay

RT:

reverse transcription

PCR:

polymerase chain reaction

SPR:

surface plasmon resonance

TDA:

target detection assay

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Acknowledgements

We thank Drs Philippe Huber (CEA-Grenoble, Grenoble, France) for 3T3 cells, Robert Auerbach (University of Madison, Madison, WI, USA) and Marco Presta (University of Brescia, Brescia, Italy) for the MBE, MAE and EOMA cells, Annunciata Vecchi (Institute of Mario Negri, Milano, Italy) for the 1G11 cells, Marc Aumercier for discussions on surface plasmon resonance and Vincent Vatin for DNA sequencing. This work was funded by the ‘Association pour la Recherche sur le Cancer’ and ‘Université de Lille II’. FL was supported by the ‘Ligue Nationale contre le Cancer’, FS is ‘Chargé de Recherche de l'Institut National de la Santé et de la Recherche Médicale’.

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  1. Etienne Lelièvre

    Present address: Center for Vascular Biology, Department of Physiology, University of Connecticut Health Center, Farmington, CT, USA

Authors and Affiliations

  1. Institut de Biologie de Lille, CNRS UMR 8526, 1 rue Calmette, Lille Cedex, 59021, France

    Frédéric Lionneton, Etienne Lelièvre, David Baillat, Dominique Stehelin & Fabrice Soncin

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Correspondence to Fabrice Soncin.

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Lionneton, F., Lelièvre, E., Baillat, D. et al. Characterization and functional analysis of the p42Ets-1 variant of the mouse Ets-1 transcription factor. Oncogene 22, 9156–9164 (2003). https://doi.org/10.1038/sj.onc.1207241

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