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Preferential Binding Sites for Interferon Regulatory Factors 3 and 7 Involved in Interferon-A Gene Transcription
- Source :
-
Journal of Molecular Biology . Mar2002, Vol. 316 Issue 5, p1009. 14p. - Publication Year :
- 2002
-
Abstract
- Transcription of the murine interferon-A4 (IFN-A4) gene is mediated by a virus responsive element (VRE-A4) located in the promoter proximal [−120 to −43] region. VRE-A4 contains four DNA modules (A to D) which cooperate for maximal IFN-A4 activation following virus infection. The differential expression between the highly expressed IFN-A4 and the weakly inducible IFN-A11 gene promoters is essentially due to point mutations within the C and D modules of the virus-responsive element VRE-A11. We now demonstrate that in murine L929 and human 293 cells, transcription factors IRF-3 and IRF-7, which are potent activators of virus-induced type I IFN transcription, differentially affect IFN-A4 and IFN-A11 promoter activities. Using electrophoretic mobility shift assays and DNase I footprinting data, our studies demonstrate that the AB modules correspond to a preferential site for IRF-7, whereas the C module is preferentially recognized by IRF-3. Furthermore, transfection of reporter constructs driven by four copies of different GAAANN hexameric motifs found within VRE-A4 indicates that the NN residues of these hexameric sequences define the preferential binding sites for IRF-3 or IRF-7. Together, these experiments clarify the molecular basis for differential expression of IFN-A genes following virus infection by delineating the sequence requirements for IRF association with the virus responsive elements of the IFN-A genes. [Copyright &y& Elsevier]
- Subjects :
- *INTERFERONS
*GENETIC regulation
*CYTOKINES
Subjects
Details
- Language :
- English
- ISSN :
- 00222836
- Volume :
- 316
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 8498071
- Full Text :
- https://doi.org/10.1006/jmbi.2001.5401