Genome-Wide Mapping of Transcriptional Regulation and Metabolism Describes Information-Processing Units in Escherichia coli

Daniela Ledezma-Tejeida, Cecilia Ishida, Julio Collado-Vides

In the face of changes in their environment, bacteria adjust gene expression levels and produce appropriate responses. The individual layers of this process have been widely studied: the transcriptional regulatory network describes the regulatory interactions that produce changes in the metabolic network, both of which are coordinated by the signaling network, but the interplay between them has never been described in a systematic fashion. Here, we formalize the process of detection and processing of environmental information mediated by individual transcription factors (TFs), utilizing a concept termed genetic sensory response units (GENSOR units), which are composed of four components: (1) a signal, (2) signal transduction, (3) genetic switch, and (4) a response. We used experimentally validated data sets from two databases to assemble a GENSOR unit for each of the 189 local TFs of Escherichia coli K-12 contained in the RegulonDB database. Further analysis suggested that feedback is a common occurrence in signal processing, and there is a gradient of functional complexity in the response mediated by each TF, as opposed to a one regulator/one pathway rule. Finally, we provide examples of other GENSOR unit applications, such as hypothesis generation, detailed description of cellular decision making, and elucidation of indirect regulatory mechanisms.