Transcription Factors Sp1 and Sp3 Regulate Basal Transcription of the Human IRF-3 Gene

Biochimie. 2012 Jun;94(6):1390-7. doi: 10.1016/j.biochi.2012.03.011. Epub 2012 Mar 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites / genetics
  • E2F1 Transcription Factor / metabolism
  • HEK293 Cells
  • Humans
  • Interferon Regulatory Factor-3 / biosynthesis*
  • Promoter Regions, Genetic / physiology
  • RNA, Messenger / metabolism
  • Sp1 Transcription Factor / physiology*
  • Sp3 Transcription Factor / physiology*
  • Transcriptional Activation / physiology

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • RNA, Messenger
  • Sp1 Transcription Factor
  • Sp3 Transcription Factor