Multi-scale molecular genetics of prokaryotic genome regulation

摘要

The molecular mechanism and regulation of transcription by DNA-binding regulatory proteins was developed using a single model prokaryote Escherichia coli. For bacterial survival in nature, however, stress-response genes are expressed in various combinations but at present, little is known how specific sets of the genes on the genome are selected for expression. Since the total number of RNA polymerase molecules in E. coli is less than the number of genes on the genome, we proposed a model that the genome expression pattern is determined by selective distribution of transcription apparatus between a total of 4,500 genes, and that the gene selectivity control of RNA polymerase is modulated after interaction of transcription factors (Fig. 1) (Ishihama 2000). We then initiated a multi-scale molecular genetics for identification of the regulatory roles of 300 species of transcription factors in E. coli (Ishihama 2009). For this purpose, we have developed ‘Genomic SELEX’ system for identification of the regulation target promoters, genes or operons by each transcription factor. Here we report the progress of on-going Genomic SELEX screening of regulation targets of E. coli transcription factors (Ishihama 2010): 1) Regulation targets have been identified for a number of uncharacterized transcription factors; 2) most of the E. coli promoters are regulated by a number of transcription factors, and some complex promoters such as the csgD promoter of the master regulator of biofilm formation are under the control of more than 10 transcription factors as in the case of eukaryotes; 2) the number of regulation targets by a single transcription factor are more than those hitherto recognized, ranging up to hundreds of genes for several global regulators such as CRP and Cra for control of the set of genes for transport and metabolism of carbon sources; and 3) the multi-factor promoters and the multi-target transcription factors form complex hierarchical networks of g--enome regulation.