Research ArticleSystems Biology

Rewiring of Transcriptional Regulatory Networks: Hierarchy, Rather Than Connectivity, Better Reflects the Importance of Regulators

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Science Signaling  02 Nov 2010:
Vol. 3, Issue 146, pp. ra79
DOI: 10.1126/scisignal.2001014

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Transcriptional Chain of Command

Systems biology leverages genomic data sets to study the properties of cellular regulatory networks and the effects of perturbation of these networks. Bhardwaj et al. organized transcriptional regulatory networks in Escherichia coli and Saccharomyces cerevisiae into pyramidal hierarchies and used existing data regarding the effect of these genes on cell fitness to show that regulators at the top of the hierarchy exerted the greatest influence. They found that having a higher position in the hierarchy better reflected influence than did the number of targets a particular regulator controlled and that changes in the network (addition of regulatory interactions or removal of nodes) affecting upper-level regulators had a larger impact on cell fitness than did changes affecting lower-level regulators. Thus, transcriptional regulatory networks appear to have an organization similar to a corporation, with top-level managers wielding the most power.

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