Transcriptional Regulatory Networks in Pancreatic Islets

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We propose to use genome-scale chromatin immunoprecipitation analysis (ChiP-on-chips) map to the transcriptional regulatory networks that control normal human pancreatic islet function. In particular, we propose to identify the promoters bound by transcription factors that play a key role in the development and function of human and murine pancreatic islets, including IPF1/Pdxl, Nkx6.1, Nkx2.2, HNF3beta/Foxa2, MafA, Isll, and NeuroDI/BETA2. By combining this information with gene expression data (EPConDB), we )lan on generating maps of active transcriptional regulatory circuitry in these cells. This information will )rovide insight into how the functional properties of the beta-cell are acquired and maintained, and will be valuable knowledge in developing cell-based approaches for treating type 1 and type 2 diabetes. Dr. Young's laboratory will provide genomics technologies and will construct the regulatory maps. Dr. Bell's laboratory will provide knowledge in beta-cell biology and expertise in isolating mouse islets and culturing beta-cell lines.