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Transcriptional induction of IFN-gamma-responsive genes is modulated by DNA surrounding the interferon stimulation response element

: Decker, T.; Strehlow, I.

Postprint (1.8 MByte; PDF; )

Nucleic Acids Research 20 (1992), No.15, pp.3865-3872
ISSN: 0305-1048
ISSN: 0301-5610
ISSN: 1362-4962
Journal Article, Electronic Publication
Fraunhofer ITA ( ITEM) ()
biological chemistry; DNA binding protein; gene expression; genetic transcription; interferon; molecular biology; Molecular genetics; regulation

The 9/27 and GBP mRNAs are both inducible by Interferon-gamma (IFN-gamma). The promoters of both genes contain an Interferon Stimulation Response Element (ISRE), but while the GBP gene is strongly induced transcriptionally by IFN-gamma the response of the 9/27 promoter is very weak. We investigated the molecular basis for this difference. The different IFN-gamma-responsiveness was found to have more than one reason. First, 9/27 promoter DNA was unable to bind the Gamma Interferon Activation Factor (GAF) with a single high affinity site. It efficiently competed for the association of the GAF with the GBP promoter but this competition was dueto the presence of two low affinity sites, the ISRE and an ISRE-like sequence, suggesting that the GAS andISRE, though both having clear preferences for specific proteins, may nevertheless share a certain degree of structural homology. (Abstract truncated).