Final Report Summary - READTHRUBACSYST (The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies) Control of transcription in bacteria is achieved at many levels, including regulation of transcription initiation and termination, as well as the availability and stability of mRNAs. While some of these mechanisms have been extensively studied and seem to be tightly controlled, transcription termination is often strikingly inefficient. Why such a central process should be inefficient is unclear, although in several cases transcriptional read-through has been reported to benefit the cell. Our aim is to investigate this process and to elucidate the role(s) of transcriptional read-through in bacterial gene regulation as well as its impact on the dynamics of genetic networks. Our approach utilizes established simple synthetic genetic networks, in which individual parameters such as induction, repression and transcriptional termination can be easily manipulated and their influence on transcription individually assessed. This experimental setting allows us to address the question of the effect of transcriptional read-through in an environment with clearly defined inputs and outputs. We show that one network built of completely identical components can produce different phenotypes depending solely on the physical position of these components relative to each other. Our results highlight the role of gene order in bacterial gene expression and its impact on the dynamics of genetic networks. We also show that gene order effects can be linked to growth rate. We suggest that in bacteria the behavior of a gene or an operon can be strongly influenced by levels and patterns of expression of its direct genetic neighborhood, and that this phenomenon serves as a source of variation underlying the diversity of phenotypes we observe.http://ist.ac.at/research/research-groups/guet-group/marie-curie-action/
