CCAAT/enhancer-binding protein-β regulates interferon-induced transcription through a novel element

Abstract

We have described previously a novel interferon (IFN)-responsive cis- acting enhancer element called γ-IFN-activated transcriptional element (GATE). GATE is distinct from the known IFN-stimulated elements and binds to novel transacting factors. To identify the γ-IFN-responsive transacting factors that interact with GATE, we have screened a cDNA expression library derived from IFN-γ-stimulated murine macrophage cell line and isolated three different cDNAs. Among these is a gene coding for the pleiotropic transcription factor, CCAAT/enhancer-binding protein-β (C/EBP-β). We report here that the gene for C/EBP-β binds to GATE and induces gene expression. A mutant C/EBP-β interferes with the IFN-γ-stimulated transcription of the ISGF3γ (p48) promoter. Other members of the C/EBP family do not cause these effects. Interestingly, the expression of C/EBP-β, not the other members of its family, is induced by IFN-γ. These studies thus identify a novel role for C/EBP-β in the IFN-signaling pathways.