CLONING AND CHARACTERIZATION OF THE HUMAN PAX2 PROMOTER

PAX2, a member of the PAX gene family of developmental transcription f actors, is expressed at high levels in the developing eyes, ears, cent ral nervous and urogenital systems, as well as in Wilms' tumor and ren al cell carcinoma. Expression of PAX2 in the urogenital system is asso ciated with proliferating cells of the ureteric bud and the differenti ating nephrogenic mesenchyme. To date, little is known about the molec ular mechanisms controlling the regulation of PAX2 expression. This re port describes the cloning and characterization of the human PAX2 gene promoter and localization of the transcription start sites in fetal k idney and Wilms' tumor. We identified two transcription start sites in a Wilms' tumor sample, which were found to be different from that in fetal kidney. The activity of a deletion series of the PAX2 promoter w as assessed in NIH-3T3, COS-7, 293, and Madin-Darby canine kidney cell s. Although some differences were observed in the activity of each pro moter construct, the profile of activity for the promoter fragment ser ies was similar in each experiment, regardless of cell type. The WT1 t umor suppressor protein, which has previously been shown to repress mu rine Pax2 expression in vitro, was shown to also repress expression fr om the human PAX2 promoter.