Abstract
We have investigated actions of the Wilms' tumour suppressor zinc finger transcription factor, WT1, on promoters of the mouse insulin-like growth factor II-encoding gene ( Igf-2). Two variant forms of WT1 repressed the two major Igf-2 promoters ( P2 and P3) in transient transfection assays. WT1-binding sites were characterised in both these promoters and in the transcribed region downstream from P2, exon 2. In each of these regions, there was a pair of WT1-binding sites, and mutational analysis of the exon-2 sites indicated that both were required for full repression. Cooperative binding of WT1 to these sites might explain the dominant-negative mutations of WT1 observed in some Wilms' tumours and Denys-Drash syndrome cases.
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