IDENTIFICATION OF DISTAL SILENCING ELEMENTS IN THE MURINE INTERFERON-A11 GENE PROMOTER

The murine interferon-A11 (Mu IFN-A11) gene is a member of the IFN-A m ultigenic family. In mouse L929 cells, the weak response of the gene's promoter to viral induction is due to a combination of both a point m utation in the virus responsive element (VRE) and the presence of nega tively regulating sequences surrounding the VRE. In the distal part of the promoter, the negatively acting E1E2 sequence was delimited. This sequence displays an inhibitory effect in either orientation or posit ion on the inducibility of a virus-responsive heterologous promoter. I t selectively represses VRE-dependent transcription but is not able to reduce the transcriptional activity of a VRE-lacking promoter. In a t ransient transfection assay, an E1E2-containing DNA competitor was abl e to derepress the native Mu IFN-A11 promoter. Specific nuclear factor s bind to this sequence thus the binding of trans-regulators participa tes in the repression of the Mu IFN-A11 gene. The E1E2 sequence contai ns an IFN regulatory factor (IRF)-binding site. Recombinant IRF2 binds this sequence and anti-IRF2 antibodies supershift a major complex for med with nuclear extracts. The protein composing the complex is 50 kDa in size, indicating the presence of IRF2 or antigenically related pro teins in the complex. The Mu IFN-A11 gene is the first example within the murine IFN-A family, in which a distal promoter element has been i dentified that can negatively modulate the transcriptional response to viral induction.