Transcription networks in C elegans organogenesis

我们的长期目标是破译后生动物系统中控制差异基因表达的机制。差异基因表达是发育的主要决定因素，转录调控不当可导致许多疾病。尽管大量的基因表达数据是可用的，但在系统水平上调控基因表达的机制知之甚少。每个基因的表达是转录激活和抑制之间的平衡，由多个转录因子（tf）控制。5-10%的后生动物基因编码tf。每个TF通过结合蛋白伴侣和靶基因DMA来调节多个靶基因的表达。多重相互作用tf

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.