A Novel Interferon-Inducible Domain: Structural and Functional Analysis of the Human Interferon Regulatory Factor 1 Gene Promoter

• Published in: Molecular and cellular biology Vol. 13; no. 1; pp. 690 - 702
• Main Authors: Sims, Simon H., Cha, Ying, Romine, Margaret F., Gao, Pei-Qing, Gottlieb, Keith, Deisseroth, Albert B.
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 01.01.1993
• ISSN: 1098-5549; 1098-5549
• DOI: 10.1128/mcb.13.1.690-702.1993

We have cloned and functionally characterized the human interferon regulatory factor 1 (IRF-1) gene promoter. The promoter contains a CpG island, with several GC boxes, a CAAT box, but no TATA box. IRF-1 mRNA is strongly induced by γ interferon (IFN-γ) but more weakly and transiently by IFN-α. There are several putative κB motifs and numerous AA(G/A)G(G/T)A and GAAANN motifs throughout the promoter. The IRF-1 promoter is not autoregulated by the IRF-1 gene product. IFN inducibility of the promoter was studied with 5' deletion mutants linked to a heterologous reporter gene. Gel mobility shift assays were used to show IFN-inducible factor binding to the IRF-1 promoter. These studies showed that IFN inducibility is conferred by a novel imperfect inverted-repeat arrangement of two GAAANN motifs within a domain, 130 nucleotides upstream of transcription initiation. This inverted repeat binds a factor upon induction with IFN and can confer IFN inducibility on a heterologous promoter. Conversely, point mutations of the inverted repeat are not IFN inducible when linked to the same heterologous promoter.