title: Upregulation of a spliced variant of human interferon regulatory factor 3 through binding of the transcription factor Sp1 to the promoter.
abstract: Interferon regulatory factor 3 (IRF-3) plays an important role in host defense against viral and bacterial infection. IRF-3 includes a variety of spliced variants, which may regulate the transcription of IRF-3. We previously identified two novel IRF-3 spliced variants, Int2V1 and Int2V2, starting from intron 2 of the wild-type of IRF-3. However, the mechanism through which the IRF-3 spliced variants regulate transcription has not been elucidated. In this study, we demonstrated that the transcription factor Sp1 upregulates the basal transcriptional activity of IRF-3 Int2V1. By transient transfection analysis, we demonstrated that the overexpression of Sp1 led to positive regulation, whereas knocking down of the endogenous Sp1 resulted in repression of IRF-3 promoter activity. Electrophoretic gel mobility shift assays and chromatin immunoprecipitation assays demonstrated that Sp1 interacted with the IRF-3 promoterin vitroandin vivo. These results suggested that Sp1 positively regulated the transcription of a spliced variant of IRF-3 through directly binding to the Sp1 consensus binding site.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Liang-Hua
authors.initials: LH
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Qiu
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhou
keywords: Sp1; interferon regulatory factor 3; reporter gene assay; spliced variant; transcription