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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4274-4281
Interferon Consensus Sequence Binding Protein and
Interferon Regulatory Factor-4/Pip Form a Complex That
Represses the Expression of the Interferon-Stimulated Gene-15 in
Macrophages
Frank Rosenbauer,
Jeffrey F. Waring,
John Foerster,
Marcus Wietstruk,
Dieter Philipp, and
Ivan Horak
From the Department of Molecular Genetics, Research Institute of
Molecular Pharmacology, and University Hospital Benjamin Franklin, Free
University of Berlin, Berlin, Germany.
Interferon consensus sequence binding protein (ICSBP), a
transcription factor of the interferon (IFN) regulatory factor (IRF) family, binds to the IFN-stimulated response element (ISRE) in the
regulatory region of IFNs and IFN-stimulated genes (ISG). To identify
target genes, which are deregulated by an ICSBP null-mutation in mice
(ICSBP /), we have analyzed transcription of an ISRE-bearing gene,
ISG15. We have found that although ISG15 expression is unchanged in B
cells, it is upregulated in macrophages from ICSBP/ mice. Three
factors, ICSBP, IRF-2, and IRF-4/Pip interact with the ISRE in B cells,
however only ICSBP and IRF-4/Pip were found to bind this sequence in
macrophages of wild-type mice. Although IRF-4 was considered to be a
lymphoid-specific factor, we provide evidence for its role in
macrophage gene regulation. Our results suggest that the formation of
cell-type-specific heteromeric complexes between individual IRFs plays
a crucial role in regulating IFN responses.
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