The role of HNF4 in gastrointestinal development

HNF4在胃肠道发育中的作用

• 批准号: 6914445
• 负责人: MICHELE A BATTLE
• 金额: $ 4.83万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6914445
• 关键词: cell differentiation; chromatin immunoprecipitation; electron microscopy; embryogenesis; gastrointestinal epithelium; gastrointestinal system; gene expression; genetically modified animals; histogenesis; histology; hormone receptor; immunocytochemistry; laboratory mouse; liver; liver cells; microarray technology; polymerase chain reaction; postdoctoral investigator; transcription factor

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.

描述（由申请人提供）： 拟议的研究的目标是确定HNF4是否对于胃肠道发育至关重要，如果HNF4是胃肠道基因表达的中心调节剂，以及HNF4是否通过调节启动子/增强子对转录激活剂的接受度的接受度来控制基因表达。先前的研究表明，HNF4是肝脏基因表达的关键介体，其在肝阻滞中消除肝细胞分化。 CRE-LoxP技术将用于在胚胎发生过程中从小鼠胃肠道的上皮细胞中有条件地去除HNF4。 HNF4在十二指肠，空肠和回肠中的损失以及横向结肠的影响将使用组织学，免疫组织学和分子技术的组合进行检查。基因阵列将用于识别其表达取决于肠道中HNF4的基因。当从肠道上皮细胞中消除HNF4时，染色质免疫沉淀分析将用于确定与肠道特异性启动子/增强子结合的因子集的变化。通过了解该转录因子如何在肠道中起作用，可以获得对肠道发育基础的基本分子过程的更深入的了解。