CCAAT/enhancer-binding protein beta mediates interferon-gamma-induced p48 (ISGF3-gamma) gene transcription in human monocytic cells

Previous studies have identified a novel interferon-stimulated response ele ment-like element, termed gamma -interferon-activating transcription elemen t, within the interferon-stimulating gene factor-3 gamma (p48) promoter reg ion that is bound by novel transcription factors in response to stimulation with interferons (IFNs) (Weihua, X,, Kolla, V., and Kalvakolanu, D, V. (19 97) Proc. Natl. Acad, Sci. U. S. A. 94, 103-108), In the present study, we have identified CCAAT/enhancer-binding protein beta (C/EBP-beta) as one of the gamma -interferon-activating transcription element cognate transcriptio n factors by screening a human monophage-derived cDNA library in a yeast on e-hybrid system. Electrophoretic mobility shift assay studies suggest that C/EBP-beta dynamically regulates p48 gene expression upon IFN-gamma stimula tion by undergoing changes in its heterodimerization partners. Transient tr ansfection studies demonstrate that overexpression of C/EBP-beta strongly e nhanced IFN-gamma -induced transcription from the p48 promoter. However, de letion mutants of C/EBP-beta that lack the N-terminal transactivation domai n were unable to stimulate the p48 promoter. Western blotting revealed that C/EBP-beta is induced by IFN-gamma stimulation in THP-1-derived macrophage s. Collectively, these results suggest that C/EBP-beta plays an important r ole in the human IFN-gamma signaling pathway by transcriptional regulation of p48 gene expression, an essential component in the IFN signaling pathway .