PMID: 8454640Mar 25, 1993Paper

Cooperative interaction between interferon (IFN) stimulus response element and kappa B sequence motifs controls IFN gamma- and lipopolysaccharide-stimulated transcription from the murine IP-10 promoter.

The Journal of Biological Chemistry
Y Ohmori, T A Hamilton

Abstract

The transcriptional regulation of the murine IP-10 gene in lipopolysaccharide (LPS) or interferon gamma (IFN gamma)-treated macrophages was investigated by analysis of regions of the gene that flank the transcription start site. A series of sequence fragments were placed 5' to the chloramphenicol acetyltransferase (CAT) reporter gene and ability to mediate transcription of CAT in response to IFN gamma or LPS treatment was studied following transient transfection in the macrophage-like cell line RAW 264.7. Analysis of larger constructs identified a potential negative regulatory site for IFN gamma response in the region between nucleotide positions -2002 and -930 and a positive regulator for LPS response in the region between bases -930 and -676. A 227-base fragment spanning positions -228 to -2 was the minimal sequence able to mediate LPS- and IFN gamma-dependent transcription of CAT. Deletion of 24 bases, which included a highly conserved IFN stimulus response element (ISRE) from the -228 construct, abolished response to IFN gamma. A 33-base fragment containing the IP-10 ISRE was able to confer both IFN gamma and LPS sensitivity upon a heterologous promoter. The ability of LPS to stimulate CAT via the ISRE was apparently mediat...Continue Reading

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