Synergism between multiple virus-induced factor-binding elements involved in the differential expression of interferon A genes.
Comparative transfection analysis of murine interferon A4 and interferon A11 promoter constructs transiently transfected in mouse L929 and human HeLa S3 cells infected with Newcastle disease virus showed that the second positive regulatory domain I-like domain (D motif), located between nucleotides -57 and -46 upstream of the transcription start site, contributes to the activation of virus-induced transcription of the interferon (IFN)-A4 gene promoter by cooperating with the positive regulatory domain I-like and TG-like domains previously described. Electrophoretic mobility shift assay performed with the virus-inducible fragments containing these motifs indicated that the binding activity that we have denoted as virus-induced factor (Génin, P., Bragança, J., Darracq, N., Doly, J., and Civas, A. (1995) Nucleic Acids Res. 23, 5055-5063) is different from interferon-stimulated gene factor 3. It binds to the D motif but not to the virus-unresponsive form of the D motif disrupted by a G-57 --> C substitution. We show that the low levels of IFN-A11 gene expression are caused essentially by the lack of two inducible enhancer domains disrupted by the A-78 --> G and the G-57 --> C substitutions. These data suggest a model taking account of the differential regulation of IFN-A gene family members. They also suggest that virus-induced factor may correspond to the primary transcription factor directly activated by virus that is involved in the initiation of IFN-A gene transcription.
Bragança
J
J
Laboratoire de Régulation de l'Expression des Gènes Eucaryotes, CNRS, UPR 37, UFR Biomédicale des Saints-Pères, Université René Descartes, Paris V, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
Génin
P
P
Bandu
M T
MT
Darracq
N
N
Vignal
M
M
Cassé
C
C
Doly
J
J
Civas
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D019281:Dimerization; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology; D016385:TATA Box; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha; C494230:Irf2 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D014764:Viral Proteins