Repression of the murine interferon alpha 11 gene: identification of negatively acting sequences.
The uninducible murine interferon alpha 11 gene (Mu IFN-alpha 11) shows strong homology with the highly inducible Mu IFN-alpha 4 gene in the promoter region. Negative regulatory sequences located between positions -470 and -145 were characterized in the Mu IFN-alpha 11 promoter. The removal of these sequences leads to virus-inducibility of Mu IFN-alpha 11 while their insertion in Mu IFN-alpha 4 corresponding region significantly reduced the inducibility of Mu IFN-alpha 4 promoter. On the other hand, the virus-responsive element (VRE) of the Mu IFN-alpha 11 differs by a single nucleotide substitution at position -78 from the VRE alpha 4. Constructions carrying either VRE alpha 11 or VRE alpha 4 upstream a heterologous promoter displayed different virus inducibilities. The -78 A/G substitution affects the inducibility by decreasing the affinity of VRE-binding trans-regulators. Our results suggest that the combined effect of the negative regulatory sequences and of the mutation in the VRE alpha 11, completely silences the Mu IFN-alpha 11 gene.
Civas
A
A
Institut de Recherches Scientifiques sur le Cancer, UPR-37 CNRS BP No. 8, Villejuif, France.
Dion
M
M
Vodjdani
G
G
Doly
J
J
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009522:Newcastle disease virus / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection / Q000235:genetics
D007370:Interferon Type I; D013937:Thymidine Kinase