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Papers In Press, published online ahead of print February 27, 2002
Oncology Center, CRB,The Johns Hopkins University, Baltimore, MD 21231-1001
Corresponding Author: parowe{at}jhmi.edu
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. Previously, we characterized human IRF-7 promoter and showed that an ISRE 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 TPA and TNFa in human peripheral blood monocytes. Using promoter analysis in combination with EMSA, we have demonstrated that an NFkB site located next to TATA box binds p50 and p65 heterodimer and is required for the induction of the IRF-7 gene by TPA and TNFa. 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 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.
J. Biol. Chem, 10.1074/jbc.M111440200
Submitted on November 30, 2001
Revised on February 5, 2002
Accepted on February 26, 2002
Stimulation of IRF-7 gene Expression by TNF alpha: Requirement for NFkB Transcription Factor and Gene Accessibility
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