The role of HNF4 in gastrointestinal development

描述（由申请人提供）： 这些研究的目的是确定HNF 4是否对胃肠道发育至关重要，HNF 4是否是胃肠道基因表达的中心调节因子，以及HNF 4是否通过调节启动子/增强子对转录激活因子的感受性来控制基因表达。先前的研究表明，HNF 4是肝脏中基因表达的关键介质，并且其在肝脏中的消除阻断肝细胞分化。Cre-loxP技术将用于在胚胎发生期间从小鼠胃肠道上皮细胞中有条件地去除Hnf 4。将使用组织学、免疫组织学和分子技术的组合来检查HNF 4在十二指肠、空肠和回肠以及横结肠中的损失的影响。基因阵列将用于鉴定其表达依赖于肠道中HNF 4的基因。染色质免疫沉淀分析将用于确定当HNF 4从肠道上皮细胞中消除时，与肠道特异性启动子/增强子结合的一组因子的变化。通过了解这种转录因子如何在肠道中发挥作用，将获得对肠道发育基础分子过程的更深入了解。

DESCRIPTION (provided by applicant): The goals of the proposed studies are to determine if HNF4 is essential for gastrointestinal development, if HNF4 is a central regulator of gastrointestinal gene expression, and if HNF4 controls gene expression by modulating the receptivity of promoters/enhancers to transcriptional activators. Previous studies have shown that HNF4 is a key mediator of gene expression in the liver and that its elimination in the liver blocks hepatocyte differentiation. Cre-loxP technology will be used to conditionally remove Hnf4 from the epithelial cells of the mouse gastrointestinal tract during embryogenesis. The effect of loss of HNF4 in the duodenum, the jejunum and ileum, and the transverse colon will be examined using a combination of histological, immunohistological, and molecular techniques. Gene arrays will be used to identify genes whose expression is dependent upon HNF4 in the gut. Chromatin immunoprecipitation analyses will be used to identify changes in the set of factors bound to gut-specific promoters/enhancers when HNF4 is eliminated from gut epithelial cells. By understanding how this transcription factor functions in the gut, greater insight into the fundamental molecular processes underlying gut development wilt be gained.