title: Effects of Four Different Regulatory Mechanisms on the Dynamics of Gene Regulatory Cascades.
abstract: Gene regulatory cascades (GRCs) are common motifs in cellular molecular networks. A given logical function in these cascades, such as the repression of the activity of a transcription factor, can be implemented by a number of different regulatory mechanisms. The potential consequences for the dynamic performance of the GRC of choosing one mechanism over another have not been analysed systematically. Here, we report the construction of a synthetic GRC in Escherichia coli, which allows us for the first time to directly compare and contrast the dynamics of four different regulatory mechanisms, affecting the transcription, translation, stability, or activity of a transcriptional repressor. We developed a biologically motivated mathematical model which is sufficient to reproduce the response dynamics determined by experimental measurements. Using the model, we explored the potential response dynamics that the constructed GRC can perform. We conclude that dynamic differences between regulatory mechanisms at an individual step in a GRC are often concealed in the overall performance of the GRC, and suggest that the presence of a given regulatory mechanism in a certain network environment does not necessarily mean that it represents a single optimal evolutionary solution.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, 2200, Denmark.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hansen
authors.affiliation: Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Bangalore, 560065, India.|Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Copenhagen, 2100, Denmark.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Krishna
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Copenhagen, 2100, Denmark.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Semsey
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, 2200, Denmark.
authors.forename: Sine
authors.initials: S
authors.lastname: Lo Svenningsen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D008954:Models, Biological; D014176:Protein Biosynthesis; D020871:RNA Stability; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins