A unique ISRE, in the TATA-less human Isg20 promoter, confers IRF-1-mediated responsiveness to both interferon type I and type II

• Published in: Nucleic acids research 2000-06, Vol.28 (12), p.2333-2341
• Main Authors: Gongora, C, Degols, G, Espert, L, Hua, T D, Mechti, N
• Format: Article
• Language: English
• Subjects: Base Sequence; Binding Sites; Biochemistry, Molecular Biology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Nucleus - metabolism; Cloning, Molecular; Conserved Sequence; DNA-Binding Proteins; Exonucleases; Exoribonucleases; Gene Expression Regulation; Genomic Library; HeLa Cells; Humans; interferon regulatory factor 1; Isg20 gene; Life Sciences; Molecular Sequence Data; Mutagenesis, Site-Directed; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Promoter Regions, Genetic; Recombinant Proteins - metabolism; Sp1 Transcription Factor - metabolism; TATA Box; Transcription Factors - metabolism; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Upstream Stimulatory Factors
• ISSN: 1362-4962; 0305-1048; 1362-4962
• DOI: 10.1093/nar/28.12.2333

Interferons (IFNs) encode a family of secreted proteins involved in a number of regulatory functions such as control of cell proliferation, differentiation and regulation of the immune system. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. We have recently isolated a human cDNA encoding a new nuclear bodies-associated protein (PML-NBs), which we have termed Isg20. In this report, we describe the cloning and functional characterization of the Isg20 promoter region and the identification of sequence elements and trans-acting factors implicated in its regulation. In the absence of any recognizable TATA or CAAT elements, Isg20 promoter basal activity is dependent upon the positive transcription factors Sp-1 and USF-1. Interestingly, we demonstrate that a unique interferon stimulated response element (ISRE) mediates both IFN type I and type II Isg20 induction in the absence of functional gamma-activated sequence. These inductions are strictly dependent upon of the IFN regulatory factor 1 (IRF-1). In addition, we show that the ISRE is also implicated in the constitutive transcriptional activity of Isg20 gene.