Cloning and functional analysis of the human IRF-3 promoter

We have isolated a genomic clone of the human IRF-3 gene containing 779 nuc leotides of the 5' flanking region and the complete intron exon sequence. T he gene has eight exons which span about 6 kb on chromosome 19q13.3. The IR F-3 promoter has neither a conserved TATA box nor a CCAAT box motif but is GC rich. Several putative DNA-binding elements were identified, including t hree SP-1 sites, a USF element, a HOX box, a CarG box, and an NF-1 site. De letion analysis of the promoter region showed that the core basal promoter, consisting of 113 bp 5' of the first transcription start site, was suffici ent for constitutive expression. This region contains only one of the SP-1 sites as well as the HOX element and NF-1 site, and although it is GC rich, it does not contain any of the other putative DNA-binding sites. Tn contra st, the mouse IRF-3 promoter, while displaying a high degree of homology wi th the human promoter, contains both TATA and CCAAT box motifs, suggesting that, at least at the level of transcription initiation, these genes may be differentially regulated.