The POU transcription factor Oct-1 represses virus-induced interferon A gene expression.
Alpha interferon (IFN-alpha) and IFN-beta 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.
Mesplède
Thibault
T
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.
Island
Marie-Laure
ML
Christeff
Nicolas
N
Petek
Fahrettin
F
Doly
Janine
J
Navarro
Sébastien
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002845:Chromatography; D004247:DNA / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D047468:Immunoprecipitation; D016898:Interferon-alpha / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D051761:Paired Box Transcription Factors / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D000998:Antiviral Agents; D016898:Interferon-alpha; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C101485:homeobox protein PITX1; D004247:DNA