CHARACTERIZATION OF THE 5'-FLANKING REGION OF THE MURINE POLYMERIC IGA RECEPTOR GENE

The regulatory elements that control basal and activated transcription al expression of the polymeric IgA receptor gene (pIgR)have not been d efined. In this study, we performed functional analysis of the murine pIgR 5'-upstream region. Transient transfection studies identified the gene's minimal promoter to reside within 110 nucleotides upstream fro m the start of transcription. Substitution mutations of this region id entified both a putative activator (- 78 to -70) and a repressor(-66 t o -52) element. DNase I footprint analysis confirmed an area of protec tion that spans from nucleotides -85 to -62. Mobility shift assays of the putative region confirmed binding of upstream stimulatory factor 1 (USF1) to an E box element at positions -75 and -70, representing the putative enhancer. Overexpression studies using various forms of USF suggest that both USF1 and USF2 enhance activity of the pIgR minimal p romoter. We report the identification and characterization of the muri ne pIgR minimal promoter as well as the critical role of USF in enhanc ing its basal level of transcription in Caco-2 cells.