Transcriptional profiling and functional genomics reveal a role for AHR transcription factor in nephrogenesis

Transcriptional profiling and functional genomics experiments using E11.5 metanephros organ cultures from Ahr(-/-) and Ahr(+/+) have shown that aryl hydrocarbon receptor (AHR) transcription factor is involved in the regulation of mesenchymal-to-epithelial transition (MET) during nephrogenesis. This response is mediated by alterations in the post-transcriptional control of Wilms' tumor suppressor (Wt1) gene and Wt1 splicing. In this article, biologically relevant gene predictor sets of the nephrogenic response were calculated for target genes of interest. The predictability of the gene set for each target was quantified by the coefficient of determination which provided a good criterion for identification of predictor sets that define the complex gene-gene interactions co-regulated by Ahr and Wt1. A subset of the signature genes was found to be co-regulated by Ahr and Wt1 and was responsible for shifts in renal cell transdifferentiation.