Stimulation of IRF-7 gene expression by tumor necrosis factor α. Requirement for NFκB transcription factor and gene accessibility

Runqing Lu, Paul A. Moore, Paula M. Pitha

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Interferon regulatory factor 7 (IRF-7) plays an important role in innate immunity, where, together with IRF-3, it controls the expression of interferon A/B genes as well as chemokine RANTES (regulated on activation normal T cell expressed and secreted). Previously, we characterized human IRF-7 promoter and showed that an interferon-stimulated response element site in the first intron binds interferon-stimulated gene factor 3 (ISGF3) and confers the response to interferon. Here we report the stimulation of IRF-7 expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor α (TNFα) in human peripheral blood monocytes. Using promoter analysis in combination with electrophoretic mobility shift assays, we have demonstrated that an NFκB site located next to the TATA box, binds p50 and p65 heterodimer and is required for the induction of the IRF-7 gene by TPA and TNFα. In addition, we report stimulation of IRF-7 gene expression by topoisomerase II (TOPII) inhibitors. We show by chromatin immunoprecipitation assay that treatment with the TOPII inhibitor etoposide induces association of acetylated histone 3 with the promoter of IRF-7 gene, indicating that TOPII-mediated changes in chromatin structure could be responsible for the induction. This suggests that the IRF-7 gene is localized in the condensed area of the chromosome where it is inaccessible to transcription factors that would promote its constitutive expression.

Original languageEnglish (US)
Pages (from-to)16592-16598
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number19
DOIs
StatePublished - May 10 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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