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THE E2/FRB PATHWAY REGULATION OF DNA REPLICATION AND PROTEIN BIOSYNTHESIS
Ward, W. O., H. Hurd, AND R. J. Duronio. THE E2/FRB PATHWAY REGULATION OF DNA REPLICATION AND PROTEIN BIOSYNTHESIS. Presented at Genetics and Environmental Mutagenesis Society, Chapel Hill, NC, November 10, 2004.
The E2F/Rb pathway plays a pivotal role in the control of cell cycle progression and regulates the expression of genes required for Gl/S transition. Our study examines the genomic response in Drosophila embryos after overexpression and mutation of E2F/Rb pathway molecules. Hierarchical clustering was used to analyze the genomic expression pattern and select genes co-expressed with established E2F target genes. These experiments have identified many genes involved in chromosome duplication, as well as novel E2F-regulated genes that are not expressed coordinately with the cell cycle during embryogenesis. A selected set of novel E2F-regulated genes were analyzed with in-situ hybridization. Some displayed expression patterns typical of E2F targets and some displayed novel patterns. The regulatory region of genes co-expressed with known E2F targets were analyzed for presence of E2F binding sites. We also demonstrate that E2f1 and Rbfl regulate the expression of ribosomal protein genes. Mutation of Elf] or Dp and overexpression of Rbfl increase and reduce ribosomal protein (RP) expression, respectively. This suggests that E2fl/Dp/Rbfl act through a common molecular mechanism, perhaps as part of a repressor complex. This complex may not act directly on RP genes since inspection of their regulatory regions did not show an enrichment of E2f binding sites. In addition, E2f1 and Rbfl also regulate the expression of Rackl, a modulator of the insulin receptor growth pathway. Thus the E2f/Rb pathway influences the expression of genes that implement and regulate cell growth.