Overlapping Elements in the Guanylate-Binding Protein Gene Promoter Mediate Transcriptional Induction by Alpha and Gamma Interferons

Abstract

The gene encoding a 67-kDa cytoplasmic guanylate-binding protein (GBP) is transcriptionally induced in cells exposed to interferon of either type I (alpha interferon [IFN-α] or INF-β) or type II (IFN-γ). The promoter of the GBP gene was cloned and found to contain an IFN-α-stimulated response element, which mediated the response of the GBP gene to IFN-α. On the basis of transfection experiments with recombinant plasmids, two different elements were delineated. Both were required to obtain the maximal response of the GBP gene to IFN-γ: the IFN-α-stimulated response element and an overlapping element termed the IFN-γ activation site. Different proteins that act on each element were investigated, and their possible involvement in IFN-γ-induced transcriptional regulation is discussed.