SILENCER ACTIVITY IN THE INTERFERON-A GENE PROMOTERS

Interferon-A (IFN-A) differential gene expression is modulated by a co mplex interplay between cis-acting DNA elements and the corresponding specific trans-regulating factors, Substitutions in the proximal virus -responsive element of the interferon-A (IFN-A) promoters contribute t o their differential gene expression, The 5' distal silencing region i n the weakly virus-inducible murine IFN-A11 gene has been previously d elimited. DNase I footprinting experiments and transient gene expressi on assays demonstrate identical silencing activity in equivalent regio ns of the genes for IFN-A11 and IFN-A4 promoters. A minimal 20-mer dis tal negative regulatory element (DNRE) in both promoters is necessary and sufficient for the silencing and a region in the highly inducible IFN-A4 promoter located between the silencer and the virus-responsive element overrides the silencer activity. Mutations in the central regi on of the DNRE, causing derepression, also altered the formation of on e of the two major DNA-protein complexes, One of these contains a prot ein related to or identical to the high mobility group I(Y) proteins, while the other complex contains a major protein present in uninduced and virus-induced cells with a molecular mass of 38 kDa, which may be related to the silencer activity. Similar DNREs are present in other v irus-uninducible IFN-A promoters, and these data suggest that a common silencer may mediate the transcriptional repression in different gene s of this family.