Study of Enhancer-Promoter Specificity in Antennapedia Complex of Drosophila

果蝇触角复合体增强子-启动子特异性的研究

• 批准号: 9874510
• 负责人: Haini Cai
• 金额: $ 42.76万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9874510&HistoricalAwards=false
• 关键词: Study; Enhancer; Promoter; Specificity; Antennapedia

The goal of this research is to understand mechanisms that regulate homeotic gene expression by specifying enhancer-promoter interactions, and to identify cis and trans factors participating in this regulation. The organization of homeotic genes is complex and poorly understood. For example, Antennapedia complex (ANT-C), a Drosophila HOM/HOX complex, contains five homeotic genes specifying segmental identity in the head and thoracic region, as well as six non-homeotic genes. These genes are controlled by arrays of enhancers located at varying distances. To understand how genes in such complex genetic loci are independently regulated, enhancer-promoter specificity will be determined for two neighboring genes, Scr and ftz, in ANT-C. Scr, a homeotic gene and ftz, a segmentation gene, are divergently transcribed and both are regulated by enhancers located within a 15 kb intergenic region. These enhancers specifically interact with their cognate promoters, directing distinct patterns of expression. Using a transgenic expression assay that allows monitoring of the activities of multiple promoters and enhancers in Drosophila embryos, it has been shown that promoter competition is probably an important mechanism for specific promoter-enhancer interaction for ftz and scr. That and other experimental observations suggest that both enhancer and promoter sequences play critical roles in specifying interactions among them and that the genomic organization of HOM/HOX complexes is important for the developmental control of homeotic gene expression. The specific questions to be asked are: 1) How does the Scr promoter specifically engage its own enhancers in the presence of the highly competitive ftz promoter 2) Is promoter competition a general mechanism for transcriptional regulation in this genomic interval? 3) What are the cis and trans factors that control the competitiveness of promoter-enhancer interactions? 4) How does insulator DNA selectively modify enhancer-promoter interactions?This study addresses a number of important issues of gene regulation in complex genetic loci and should provide insights into genetic regulatory strategies used in body pattern formation in animals including humans.

这项研究的目的是了解通过指定增强子促进剂相互作用，并识别参与该调节的顺式和反式因素来了解调节同源基因表达的机制。同源基因的组织是复杂的，知之甚少。例如，一种果蝇（果蝇）抗果蝇（ANT-C），一种果蝇/HOX复合物，包含五个指定头部和胸部区域中分段身份的同源基因，以及六个非植菌基因。这些基因由位于不同距离的增强子阵列控制。为了了解如何独立调节这种复杂的遗传基因座中的基因，将确定两个相邻基因SCR和FTZ的增强子促销特异性。 SCR，一个同源基因和FTZ（一种分割基因）被分解转录，并且两者都由位于15 kb的基因间区域内的增强子进行调节。这些增强子特异性与其同源启动子相互作用，指导了不同的表达模式。使用允许监测果蝇胚胎中多个启动子和增强子活性的转基因表达测定法，已经表明启动子竞争可能是FTZ和SCR的特定启动子增强剂相互作用的重要机制。 这和其他实验观察结果表明，增强子和启动子序列在指定它们之间的相互作用方面起着关键作用，而HOM/HOX复合物的基因组组织对于均基因表达的发展控制很重要。要问的具体问题是：1）在竞争激烈的FTZ启动子的存在下，SCR启动子如何专门参与其自己的增强子2）启动子竞争是在此基因组间隔内进行转录调控的一般机制？ 3）控制启动子增强剂相互作用的竞争力的顺式和反式因素是什么？ 4）绝缘体DNA如何选择性地修改增强子促进剂的相互作用？本研究解决了复杂遗传基因座中基因调控的许多重要问题，并应提供对在包括人类在内的动物人体模式形成中使用的遗传调节策略的见解。