Our project seeks to identify the regulatory elements recognized by essentially all of transcription factors (TFs) in the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans. Transcription factors (TFs) play key roles in diverse aspects of development and physiology. A catalog of sites where transcription factors bind (regulatory sequences) is perhaps only second in importance to a catalog of genes in understanding how a genome specifies an organism. First as part of modENCODE and over the past grant cycle as the independent modern program, we will have generated about 800 ChIP-seq profiles (440 worm, 380 fly) for more than 600 transcription factors (280 worm, 340 fly). Building on this progress in this proposal we seek: 1) to complete an initial catalog of binding sites for all transcription factors in both D. melanogaster and C. elegans; 2) to validate these sites through measuring the impact of transcription factor loss on the expression of genes; 3) to integrate binding sites and gene expression profiles both with one another and with other available information to develop models of gene expression and gene regulatory networks. All of the strain resources and data will be made publicly available on a timely basis throughout the project. These catalogs will represent the first comprehensive description of the TF binding sites in any metazoan and will provide a context for understanding the catalog of TF binding sites that will emerge from ENCODE.
Insights from the study of the model organisms Drosophila and C. elegans provide the basis for broad understanding of fundamental processes of animal biology. Because many of their genes have clear relatives in humans, these studies have also led directly to improved understanding of human diseases and in some cases to therapies. Similarly, creating a comprehensive understanding of transcription factor binding sites and building regulatory networks in these key model organisms will create the foundation for understanding human regulatory networks both in health and disease.
