The interplay of digital, analog and metabolic control in gene expression patterns

Recently we have analyzed the correspondence between gene expression patterns and the transcriptional regulatory network (TRN) of wild type E. coli and mutants lacking structural proteins (Marr et al. 2008). The expression changes have been induced by a change in supercoiling energy. With this general setup we aimed at comparing the amount of network control on gene expression levels with the amount of structural control (represented by correlated changes of neighboring genes on the genome). We compared the regulation mediated by gene-gene interactions through dedicated transcription factors on the one hand, with the continuous regulation of neighboring genes on the chromosome by alteration of the superhelical density, on the other. We termed the two control types digital (referring to the fact that the TRN provides static information on the connections between unique, discontinuous components, e.g. a particular pair of regulator and regulated gene) and analog (referring to the fact that the expression of specific genes is under the control of continuous information provided by distributions of supercoiling energy in the genome), respectively. We observed an increase in digital control when going from wild type to mutants, and at the same time a decrease in analog control, suggesting (1) that control in wild type is predominantly analog (i.e. mediated by DNA topology) and (2) that the two types of control are evolutionarily interlinked and buffer each other upon perturbation of the system. Within this presentation, these findings are reviewed and put into the context of robust system functioning. Marr, C., Geertz, M., Hütt, M.-Th. and Muskhelishvili, G. (2008) Dissecting the logical types of network control in gene expression profiles, BMC Systems Biology 2, 18.

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