Repression of promoters for the mouse insulin-like growth factor II-encoding gene (Igf-2) by products of the Wilms' tumour suppressor gene wt1.
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.
Ward
A
A
Department of Zoology, University of Oxford, UK.
Pooler
J A
JA
Miyagawa
K
K
Duarte
A
A
Hastie
N D
ND
Caricasole
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*; D025721:WT1 Proteins
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D007335:Insulin-Like Growth Factor II