title: Transcription factors Sp1 and Sp3 regulate basal transcription of the human IRF-3 gene.
abstract: Interferon regulatory factor 3 (IRF-3) plays a crucial role in initiation and development of the IFN antiviral response. The expression level of human IRF-3 is thought to be closely related to antiviral state of cells. However, the mechanisms of the transcription regulation of IRF-3 have remained largely unknown. We previously reported that transcription factor E2F1 negatively regulates the basal transcriptional activity of IRF-3. Here we demonstrate that transcription factors Sp1 and Sp3 up-regulate the basal transcriptional activity of IRF-3 and increase IRF-3 expression at mRNA level. By transient transfection analysis we revealed that mutation of Sp1/NRF-1 binding site resulted in a profound reduction of IRF-3 promoter activity. Overexpression of Sp1 and Sp3, but not NRF-1, transactivated the IRF-3 promoter activity in reporter gene assays while knocking-down of endogenous Sp1 and Sp3 by a shRNA strategy markedly inhibited IRF-3 promoter activity. Chromatin immunoprecipitation (ChIP) assays showed that Sp1 and Sp3 interact with the IRF-3 promoter in vivo. These results suggest that basal expression level of IRF-3 is regulated by transcription factors Sp1 and Sp3.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
authors.forename: Hua-Guo
authors.initials: HG
authors.lastname: Xu
authors.forename: Rui
authors.initials: R
authors.lastname: Jin
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhou
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000502:physiology*; D051705:Sp3 Transcription Factor / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor