Internal versus external effector and transcription factor gene pairs differ in their relative chromosomal position...

Transcription factors (TFs) play an important role in the genetic regulation of transcription in response to internal and external cellular stimuli. However, little is known about their functional and dynamic aspects on a large scale, even in a well-studied bacterium like Escherichia coli. To understand the regulatory dynamics and to improve our knowledge about how TFs respond to endogenous and exogenous signals in this simple bacterium model, we previously proposed that TFs can be classified into three classes, depending on how they sense their allosteric or equivalent metabolite: external class, internal class, and hybrid sensing class. Classification of these groups was done without considering the relative chromosomal positions of the TFs and their corresponding effector genes. Here, we analyze the genome organization of the genetic components of these sensing systems, using the classification described earlier. We report the chromosomal proximity of transcription factors and their effector genes to sense periplasmic signals or transported metabolites (i.e. transcriptional sensing systems from the external class) in contrast to the components for sensing internally synthesized metabolites, which tend to be distant on the chromosome. We strengthen our finding that external sensing genetic machinery behaves like chromosomal modules of regulation to respond rapidly to variations in external conditions through co-expression of their genetic components, which is corroborated with microarray data for E. coli. Furthermore, we show several lines of evidence supporting the need for the coordinated activity of external sensing systems in contrast to that of internal sensing machinery, which can explain their close chromosomal organization. The observed functional correlation between the chromosomal organization and the genetic machinery for environmental sensing should contribute to our understanding of the logical functioning and evolution of the transcriptional regulatory networks in bacteria.