Transcription networks in C elegans organogenesis

线虫器官发生中的转录网络

• 批准号: 7619293
• 负责人: A. J. Marian Walhout
• 金额: $ 30.95万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-10-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7619293
• 关键词: Binding; Biochemical Genetics; Biological; Caenorhabditis elegans; Computer Systems Development; DNA-Protein Interaction; Data; Data Analyses; Databases; Development; Disease; Equilibrium; Gene Expression; Gene Targeting; Genes; Genetic Transcription; Goals; Homeostasis; Homologous Gene; Imagery; Intestines; Lead; Maps; Methods; Modeling; Nematoda; Organ; Organogenesis; Play; Property; Proteins; Regulatory Element; Repression; Research Personnel; Role; System; Tissue-Specific Gene Expression; Tissues; Transcriptional Activation; Transcriptional Regulation; Validation; Whole Organism; biological systems; computerized tools; genome-wide; insight; novel; programs; promoter; protein protein interaction; transcription factor; yeast two hybrid system

Our long-term goal is to decipher the mechanisms that control differential gene expression in metazoan systems. Differential gene expression is a major determinant in development, and misregulation of transcription can lead to numerous diseases. Although vast amounts of gene expression data are available, little is known about the mechanisms that regulate gene expression at a systems level. The expression of each gene is a balance between transcription activation and repression, governed by multiple transcription factors (TFs). Between 5-10% of metazoan genes encode TFs. Each TF regulates the expression of multiple target genes by binding both to protein partners and to target gene DMA. The multiple interactions TFs engage in, and the concerted action of multiple TFs per gene suggests that differential gene expression is the result of intricate transcription regulatory networks (TRNs) in which many TFs are functionally connected. The general aim of this proposal is to map TRNs that control intestinal development in the nematode Caenhorhabditis elegans. C. elegans intestinal development is an excellent system to understand differential gene expression because genome-wide intestinal expression data are available and because transcription regulation plays a pivotal role in this tissue. We will identify intestinal TRNs by mapping protein-DNA and protein-protein interactions involving intestinal promoters and TFs using high-throughput yeast one -and two-hybrid systems. We will generate a database for data tracking, data analysis and to make the data publicly available. To validate interactions, we will manually and computationally integrate protein interactions with available gene expression and phenotypic data. In addition, we will initiate the validation of protein interactions by experimental methods. The mapping of intestinal TRNs will reveal transcriptional mechanisms that underlie differential gene expression in intestinal development. Since this is a conserved biological program, these TRNs may provide insights into mammalian differential gene expression as well.

我们的长期目标是破译控制后生动物系统中差异基因表达的机制。差异基因表达是发育中的主要决定因素，转录的正调可能导致许多疾病。尽管可以使用大量的基因表达数据，但对调节基因表达在系统级别的机制知之甚少。每个基因的表达是由多个转录因子（TFS）控制的转录激活和抑制之间的平衡。在5-10％的后生基因编码TF之间。每个TF通过与蛋白质伴侣和靶向基因DMA结合来调节多个靶基因的表达。多个互动TFS 参与每个基因的多个TF的协同作用表明，差异基因表达是复杂的转录调节网络（TRN）的结果，其中许多TF在功能上连接。 该提案的一般目的是绘制控制线虫秀丽隐杆线虫中肠道发育的TRN。秀丽隐杆线虫的肠道发育是理解差异基因表达的绝佳系统，因为全基因组肠道表达数据可获得，并且因为转录调节在该组织中起关键作用。我们将通过绘制涉及肠道启动子和TF的蛋白质-DNA和蛋白质 - 蛋白质相互作用来鉴定肠道TRN，并使用高通量酵母菌和两个杂交系统来鉴定肠道TRN。我们将生成一个数据库，用于数据跟踪，数据分析并使数据公开可用。为了验证相互作用，我们将手动和计算与可用的基因表达和表型数据整合蛋白质相互作用。此外，我们将启动蛋白质的验证 通过实验方法进行的相互作用。肠道TRN的映射将显示转录 肠发展中差异基因表达的机制。由于这是一个保守的生物学程序，因此这些TRN也可以提供对哺乳动物差异基因表达的见解。