Multi-Scale Genetics towards Understanding the Hierarchy of Transcription Factor Network in Genome Regulation

The model bacterium, Escherichia coli, is able to survive under various stressful conditions in nature. From the complete genome sequence, about 4,400 genes are considered to exist on the genome. Selective and regulated expression of the genes is critical for bacterial adaptation to environment. Since the number of RNA polymerase, the enzyme responsible for transcription, is less than that of total genes, we proposed that the controlled distribution of RNA polymerase among 4,400 genes determines the genome expression pattern. In order to understand the molecular basis of genome regulation, we have been concerned with the analysis of all 300 transcription factors, which are involved in the functional modulation of RNA polymerase for switching the gene selectivity. For this purpose, we have performed the systematic search for target genes and promoters recognized by each transcription factor using the newly developed genomic SELEX system. Here we describe some results of this multi-scale genetics focusing on the protein-protein and protein-DNA interaction networks involved in the genome regulation. One hitherto undescribed finding is that the transcription factors form interplay networks, in which one transcription factor controls the expression of another factor and so on. The putative transcription factors with unidentified functions are often located on top of the hierarchy of transcription factor cascade. Such networks appear to be needed for stress response in nature