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J. Biol. Chem., Vol. 277, Issue 19, 16592-16598, May 10, 2002
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B TRANSCRIPTION FACTOR AND GENE
ACCESSIBILITY*
§,
From the 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 The Sidney Kimmel Comprehensive Cancer
Center and the Department of Molecular Biology and Genetics,
The Johns Hopkins University School of Medicine, Baltimore, Maryland
21231 and the ¶ Human Genome Sciences, Inc.,
Rockville, Maryland 20850
(TNF) in human peripheral blood
monocytes. Using promoter analysis in combination with electrophoretic
mobility shift assays, we have demonstrated that an NFB 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 TNF. 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.
To whom correspondence should be addressed: The
Bunting and Blaustein Cancer Research Bldg., Rm. 351, The Johns
Hopkins University, 1650 Orleans St., Baltimore, MD 21231-1001. E-mail: parowe@jhmi.edu.
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