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Molecular and Cellular Biology, October 2005, p. 8717-8731, Vol. 25, No. 19
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.19.8717-8731.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Laboratoire de Régulation de la Transcription et Maladies Génétiques, CNRS, UPR 2228,1 Laboratoire de Régulation de la Transcription des Gènes Eucaryotes, UPR 37, UFR Biomédicale des Saints-Pères, Université René Descartes, 45 Rue des Saints-Pères, 75270 Paris Cedex 06, France2
Received 21 January 2005/ Returned for modification 5 April 2005/ Accepted 11 July 2005
Alpha interferon (IFN-
) and IFN-ß are able to interfere with viral infection. They exert a vast array of biologic functions, including growth arrest, cell differentiation, and immune system regulation. This regulation extends from innate immunity to cellular and humoral adaptive immune responses. A strict control of expression is needed to prevent detrimental effects of unregulated IFN. Multiple IFN-A subtypes are coordinately induced in human and mouse cells infected by virus and exhibit differences in expression of their individual mRNAs. We demonstrated that the weakly expressed IFN-A11 gene is negatively regulated after viral infection, due to a distal negative regulatory element, binding homeoprotein pituitary homeobox 1 (Pitx1). Here we show that the POU protein Oct-1 binds in vitro and in vivo to the IFN-A11 promoter and represses IFN-A expression upon interferon regulatory factor overexpression. Furthermore, we show that Oct-1-deficient MEFs exhibit increased in vivo IFN-A gene expression and increased antiviral activity. Finally, the IFN-A expression pattern is modified in Oct-1-deficient MEFs. The broad representation of effective and potent octamer-like sequences within IFN-A promoters suggests an important role for Oct-1 in IFN-A regulation.
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