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（芯片上芯片）图 控制正常人类胰岛功能的转录调控网络。特别地，我们提出鉴定在人类和鼠胰岛的发育和功能中起关键作用的转录因子结合的启动子，所述转录因子包括IPF 1/Pdx 1、Nkx6.1、Nkx2.2、HNF 3beta/Foxa 2、MafA、Isll和NeuroDI/BETA2。通过将这些信息与基因表达数据（EPConDB）相结合，我们将绘制这些细胞中活性转录调控电路的图谱。这些信息将有助于深入了解β细胞的功能特性是如何获得和维持的，并且将是开发用于治疗1型和2型糖尿病的基于细胞的方法的有价值的知识。 博士杨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β细胞生物学知识和分离小鼠胰岛和培养β细胞系的专业知识。

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.