Activation of the WT1 Tumor Suppressor Gene Promoter by Pea3

Gene array profiling of RNA from cells engineered to express a dominant-negative version of the ETS family member transcription factor Pea3 (polyomavirus enhancer activator 3) identified WT1 as a candidate downstream gene. Given the co-expression of WT1 and Pea3 in developing kidney and breast tissue undergoing mesenchymal to epithelial transitions, we further characterized this potential gene hierarchy. Analysis of the human WT1 promoter revealed several potential binding sites for Pea3. Pea3 transactivated the WT1 promoter in transient transfection assays and bound to specific sites within the WT1 promoter in vitro. Our results position Pea3 upstream of WT1 and define a gene hierarchy important for mesenchymal-epithelial transitions.