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HNF4是否对胃肠道发育是必需的，HNF4是否是胃肠道基因表达的中央调节因子，以及HNF4是否通过调节启动子/增强子对转录激活剂的接受性来控制基因表达。以前的研究表明，HNF4是肝脏基因表达的关键介质，它在肝脏中的消除阻止了肝细胞的分化。Cre-loxP技术将用于在胚胎发育期间有条件地从小鼠胃肠道上皮细胞中去除Hnf4。HNF4在十二指肠、空肠、回肠和横结肠丢失的影响将通过组织学、免疫组织学和分子技术相结合的方法进行检测。基因阵列将用于识别其表达依赖于肠道中HNF4的基因。染色质免疫沉淀分析将被用来确定当HNF4从肠道上皮细胞中消除时，与肠道特异性启动子/增强剂结合的一组因子的变化。通过了解这种转录因子在肠道中的功能，可以更深入地了解肠道发育的基本分子过程。

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.