Transcriptional Regulatory Networks in Pancreatic Islets

描述（由申请人提供）： 我们建议使用基因组规模的染色质免疫沉淀分析（ChIP芯片）映射的转录调控网络，控制正常的人类胰岛功能。特别是，我们建议确定转录因子，包括HNF 3 β，IPF-1，NKX6.1，NKX2.2，PAX 4，ISL 1和NEUROD 1的发展和功能中发挥关键作用的启动子结合。通过将这些信息与基因表达数据（EPConDB）相结合，我们计划在这些细胞中生成活性转录调控电路的地图。这些信息将提供深入了解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。

DESCRIPTION (provided by applicant): We propose to use genome-scale chromatin immunoprecipitation analysis (ChIP-on-chips) to map 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 HNF3beta, IPF-1, NKX6.1, NKX2.2, PAX4, ISL1, and NEUROD1. By combining this information with gene expression data (EPConDB), we plan on generating maps of active transcriptional regulatory circuitry in these cells. This information will provide 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.