We propose to use newly developed experimental and computational technologies to begin mapping the transcriptional regulatory networks that control the cell cycle in human cells. It is fundamentally important to understand these regulatory networks, as many biological processes and diseases are connected in some manner to cell cycle control. Transcriptional regulatory networks can be mapped by identifying the sites bound by regulators throughout the genome of living cells, and by combining this information with gene expression data. To accomplish this, the specific aims of the proposal are: 1) Determine the genomic binding sites of candidate cell cycle transcriptional regulators in human cells; 2) Identify the set of human genes whose expression oscillates during the cell cycle in human cells; 3) Construct a model of the transcriptional regulatory network that controls the human cell cycle and test its key features; and 4) Identify differences between cell cycle regulation in primary fibroblasts and fibroblast tumor cells. The transcriptional regulatory networks that control the human cell cycle will be of fundamental value to biologists because they will reveal pathways by which cellular phenotypes are regulated and may suggest new strategies to diagnose and combat diseases associated with defects in cell cycle regulation.
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