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.
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.
Rosenbauer
F
F
Department of Molecular Genetics, Research Institute of Molecular Pharmacology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany.
Waring
J F
JF
Foerster
J
J
Wietstruk
M
M
Philipp
D
D
Horak
I
I
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D050835:Interferon Regulatory Factors; D007372:Interferons / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014452:Ubiquitins; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
D016207:Cytokines; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D007372:Interferons; D012097:Repressor Proteins; D014157:Transcription Factors; D014452:Ubiquitins; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4; C489550:G1p2 protein, mouse