The virus-induced factor VIF differentially recognizes the virus-responsive modules of the mouse IFNA4 gene promoter.
Maximal activation of murine infection-A4 (IFNA4) gene transcription following viral infection requires the presence of four cooperating DNA sequences (denoted A to D), which make up the virus responsive element VRE-A4. The B, C, and D modules, when tandemized, form binding sites for the virus-induced factor (VIF), a multiprotein complex that is detected early after viral infection in the nuclei of mouse L929 cells. We now demonstrate that IFN regulatory factor-3 (IRF-3) is a component of VIF and that VIF is different from the previously identified virus-activated complexes containing IRF-3 and coactivators of transcription, such as CREB binding protein (CBP) or p300. We also show that the C module is critical for both IRF-3-mediated and virus-induced transcription of the murine IFNA4 gene. Consistently, DNase I footprinting experiments and EMSA performed with increasing amounts of recombinant GST-IRF-3(DBD) fusion proteins demonstrate that cooperativity between the modules facilitate the binding of IRF-3 and recruitment of transcription coactivators on the IFNA4 promoter. These results indicate that VIF differentially recognizes the virus-responsive modules of VRE-A4 and further actualize our previous model concerning the differential expression of murine IFNA genes.
Morin
Pierre
P
UPR 2228-CNRS, Régulation Transcriptionnelle et Maladies Génétiques, UFR Biomédicale des Saints-Pères, Université Paris V, 75270 Paris Cedex 06, France.
Génin
Pierre
P
Doly
Janine
J
Civas
Ahmet
A
D000818:Animals; D001483:Base Sequence; D050882:CREB-Binding Protein; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D050881:E1A-Associated p300 Protein; D006801:Humans; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009522:Newcastle disease virus / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020218:Response Elements; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; C494233:Irf3 protein, mouse; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse