PMID:7720589

Citation	Ryan, G, Steele-Perkins, V, Morris, JF, Rauscher, FJ 3rd and Dressler, GR (1995) Repression of Pax-2 by WT1 during normal kidney development. Development 121:867-75
Abstract	The developmental, regulatory gene Pax-2 is activated during early kidney morphogenesis and repressed in mature renal epithelium. Persistent Pax-2 expression is also observed in a variety of kidney tumors. Yet, little is known about the signals regulating this transient expression pattern in the developing kidney. We have examined the spatial and temporal expression patterns of Pax-2 and the Wilm's tumor suppresser protein WT1 with specific antibodies in developing mouse kidneys. A marked increase in WT1 protein levels coincided precisely with down-regulation of the Pax-2 gene in the individual precursor cells of the visceral glomerular epithelium, suggesting a direct effect of the WT1 repressor protein on Pax-2 regulatory elements. To examine whether WT1 could directly repress Pax-2 transcription, binding of WT1 to three high affinity sites in the 5' untranslated Pax-2 leader sequence was demonstrated by DNAseI footprinting analysis. Furthermore, co-transfection assays using CAT reporter constructs under the control of Pax-2 regulatory sequences demonstrated WT1-dependent transcriptional repression. These three WT1 binding sites were also able to repress transcription, in a WT1-dependent manner, when inserted between a heterologous promoter and the reporter gene. The data indicate that Pax-2 is a likely target gene for WT1 and suggest a direct link, at the level of transcriptional regulation, between a developmental control gene, active in undifferentiated and proliferating cells, and a known tumor suppressor gene.
Links	PubMed
Keywords	Animals; Base Sequence; DNA-Binding Proteins/genetics; Gene Expression Regulation, Developmental; Genes, Regulator; Genetic Techniques; Kidney/embryology; Mice; Mice, Inbred Strains; Molecular Sequence Data; Morphogenesis/genetics; PAX2 Transcription Factor; Transcription Factors/genetics; WT1 Proteins; Zinc Fingers/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:WT1	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P32114	F		Seeded From UniProt	complete
HUMAN:WT1	enables	GO:0043565: sequence-specific DNA binding	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:WT1	involved_in	GO:0045892: negative regulation of transcription, DNA-templated	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:EGR1	involved_in	GO:0045893: positive regulation of transcription, DNA-templated	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PAX2	enables	GO:0070742: C2H2 zinc finger domain binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P19544	F		Seeded From UniProt	complete

References

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