An ATF/CREB binding site is required for virus induction of the human interferon beta gene [corrected]

We report the characterization of a distinct regulatory element of the human interferon beta (HuIFN-beta) gene promoter, which we designate PRDIV (positive regulatory domain IV). In previous studies, sequences between -104 and -91 base pairs upstream from the start site of transcription were shown to be required for maximal levels of virus induction in mouse L929 cells. We have localized the essential sequence in this region extending from -99 to at least -91, and we show that this sequence is a binding site for a protein of the activating transcription factor/cAMP response element binding protein (ATF/CREB) family of transcription factors. Mutations in PRDIV that decrease the affinity of one member of this family (ATF-2/CRE-BP1) decrease the level of virus induction in vivo. Moreover, multiple copies of PRDIV can confer both virus and cAMP inducibility upon a minimal promoter in L929 cells, while it is constitutively active in HeLa cells. We conclude that PRDIV is a distinct regulatory element of the HuIFN-beta promoter and that the signal transduction pathways involved in virus and cAMP induction may partially overlap.