Transcriptional Profiling and Functional Genomics Reveal a Role for AHR Transcription Factor in Nephrogenesis

Abstract:  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.

摘要：对来自Ahr - / - 和Ahr + / +的E11.5后肾器官培养物进行的转录谱分析和功能基因组学实验表明，芳香烃受体（AHR）转录因子在肾发生过程中参与间充质 - 上皮转化（MET）的调节。这种反应是由威尔姆斯肿瘤抑制基因（Wt1）的转录后调控以及Wt1剪接的改变所介导的。在本文中，针对感兴趣的靶基因计算了肾发生反应的生物学相关基因预测集。通过决定系数对每个靶基因集的可预测性进行量化，这为鉴定定义由Ahr和Wt1共同调控的复杂基因 - 基因相互作用的预测集提供了一个良好的标准。发现特征基因的一个子集由Ahr和Wt1共同调控，并负责肾细胞转分化的转变。