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Molecular and Cellular Biology, October 2000, p. 7527-7540, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Repression of Virus-Induced Interferon A Promoters by Homeodomain Transcription Factor Ptx1

Sébastien Lopez,1 Marie-Laure Island,1 Jacques Drouin,2 Marie-Thérese Bandu,1 Nicolas Christeff,1 Nicole Darracq,1 Régine Barbey,3 Janine Doly,1 Dominique Thomas,3 and Sébastien Navarro1,*

Laboratoire de Régulation de la Transcription et Maladies Génétiques, CNRS, UPR 2228, UFR Biomédicale des Saints-Pères, Université René Descartes, 75270 Paris Cedex 06,1 and Centre Génétique Moléculaire, CNRS, 91198 Gif-sur-Yvette Cedex,3 France, and Laboratoire de Génétique Moléculaire, Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada H2W 1R72

Received 27 April 2000/Returned for modification 16 June 2000/Accepted 21 July 2000

Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by substitutions in the proximal positive virus responsive element A (VRE-A) of their promoters and by the presence or absence of a distal negative regulatory element (DNRE). The functional feature of the DNRE is to specifically act by repression of VRE-A activity. With the use of the yeast one-hybrid system, we describe here the identification of a specific DNRE-binding protein, the pituitary homeobox 1 (Ptx1 or Pitx1). Ptx1 is detectable in different cell types that differentially express IFN-A genes, and the endogenous Ptx1 protein binds specifically to the DNRE. Upon virus induction, Ptx1 negatively regulates the transcription of DNRE-containing IFN-A promoters, and the C-terminal region, as well as the homeodomain of the Ptx1 protein, is required for this repression. After virus induction, the expression of the Ptx1 antisense RNA leads to a significant increase of endogenous IFN-A gene transcription and is able to modify the pattern of differential expression of individual IFN-A genes. These studies suggest that Ptx1 contributes to the differential transcriptional strength of the promoters of different IFN-A genes and that these genes may provide new targets for transcriptional regulation by a homeodomain transcription factor.

* Corresponding author. Mailing address: Laboratoire de Régulation de la Transcription et Maladies Génétiques, CNRS, UPR 2228, UFR Biomédicale des Saints-Pères, Université René Descartes, 45 Rue des Saints-Pères, 75270 Paris Cedex 06, France. Phone: 33- 1-42-86-22-73. Fax: 33-1-42-86-20-42. E-mail: Sebastien.Navarro{at}biomedicale.univ-paris5.fr.

Molecular and Cellular Biology, October 2000, p. 7527-7540, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Mesplede, T., Island, M.-L., Christeff, N., Petek, F., Doly, J., Navarro, S. (2005). The POU Transcription Factor Oct-1 Represses Virus-Induced Interferon A Gene Expression. Mol. Cell. Biol. 25: 8717-8731 [Abstract] [Full Text]  
  • Island, M.-L., Mesplede, T., Darracq, N., Bandu, M.-T., Christeff, N., Djian, P., Drouin, J., Navarro, S. (2002). Repression by Homeoprotein Pitx1 of Virus-Induced Interferon A Promoters Is Mediated by Physical Interaction and trans Repression of IRF3 and IRF7. Mol. Cell. Biol. 22: 7120-7133 [Abstract] [Full Text]  
  • Barnes, B. J., Moore, P. A., Pitha, P. M. (2001). Virus-specific Activation of a Novel Interferon Regulatory Factor, IRF-5, Results in the Induction of Distinct Interferon alpha Genes. J. Biol. Chem. 276: 23382-23390 [Abstract] [Full Text]  


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