Transcriptional Regulatory Networks in Pancreatic Islets

我们建议使用基因组规模的染色质免疫沉淀分析(芯片上的芯片)图谱 控制正常人类胰岛功能的转录调控网络。特别是，我们建议确定在人和小鼠胰岛的发育和功能中发挥关键作用的转录因子结合的启动子，包括IPF1/Pdx1、Nkx6.1、Nkx2.2、HNF3beta/Foxa2、Mafa、Isll和NeuroDI/beta2。通过将这些信息与基因表达数据(EPConDB)相结合，我们可以在这些细胞中生成活跃的转录调控电路图谱。这些信息将为深入了解β细胞的功能特性是如何获得和维持的，并将是开发基于细胞的方法治疗1型和2型糖尿病的宝贵知识。 杨博士的实验室将提供基因组学技术，并将构建监管地图。贝尔博士的实验室将提供贝塔细胞生物学方面的知识，以及分离小鼠胰岛和培养贝塔细胞系方面的专业知识。

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.