Increased levels of interferon regulatory element-binding activities in nuclei of high interferon-producing If-1h mice.

The transient induction of type I interferon (IFN) genes following a viral infection involves transcriptional derepression and activation, mediated by positive and negative factors which bind to upstream cis-acting elements. We have transfected the human IFN-beta gene into primary splenocytes from mice regulated by the If-1 locus and have shown that the exogenous gene is regulated by this locus in a manner similar to that of endogenous IFN genes. Using nuclear extracts from splenocytes of C57BL/6 (If-1h) and BALB/c (If-1l) mice in gel retardation assays, we found that levels of DNA-binding activities for the interferon regulatory element and its subelements were constitutive in nuclear extracts of spleen cells. Levels of DNA binding to the interferon regulatory element were higher in extracts from the nuclei of If-1h mice and thus correlate with the higher levels of human IFN-beta mRNA detected in these transfected cells and the transcription of the endogenous IFN genes. Higher levels of DNA-binding/transcription factors found in nuclei from spleen cells of If-1h mice may be involved in the expression of the If-1 phenotype.