From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in Escherichia coli.

Because a large number of molecular mechanisms involved in gene regulation have been described during the last decades, it is now becoming possible to address questions about the global structure of gene regulatory networks, at least in the case of some of the best-characterized organisms. This paper presents a global characterization of the transcriptional regulation in Escherichia coli on the basis of the current data. The connectivity of the corresponding network was evaluated by analyzing the distribution of the number of genes regulated by a given regulatory protein, and the distribution of the number of regulatory genes regulating a given regulated gene. The mean connectivity found (between 2 and 3) shows a rather loosely interconnected structure. Special emphasis is given to circular sequences of interactions ("circuits") because of their critical dynamical properties. Only one-element circuits were found, in which negative autoregulation is the dominant architecture. These global properties are discussed in light of several pertinent theoretical approaches, as well as in terms of physiological and evolutionary considerations.