Assigning numbers to the arrows: parameterizing a gene regulation network by using accurate expression kinetics.
A basic challenge in systems biology is to understand the dynamical behavior of gene regulation networks. Current approaches aim at determining the network structure based on genomic-scale data. However, the network connectivity alone is not sufficient to define its dynamics; one needs to also specify the kinetic parameters for the regulation reactions. Here, we ask whether effective kinetic parameters can be assigned to a transcriptional network based on expression data. We present a combined experimental and theoretical approach based on accurate high temporal-resolution measurement of promoter activities from living cells by using green fluorescent protein (GFP) reporter plasmids. We present algorithms that use these data to assign effective kinetic parameters within a mathematical model of the network. To demonstrate this, we employ a well defined network, the SOS DNA repair system of Escherichia coli. We find a strikingly detailed temporal program of expression that correlates with the functional role of the SOS genes and is driven by a hierarchy of effective kinetic parameter strengths for the various promoters. The calculated parameters can be used to determine the kinetics of all SOS genes given the expression profile of just one representative, allowing a significant reduction in complexity. The concentration profile of the master SOS transcriptional repressor can be calculated, demonstrating that relative protein levels may be determined from purely transcriptional data. This finding opens the possibility of assigning kinetic parameters to transcriptional networks on a genomic scale.
Ronen
Michal
M
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Rosenberg
Revital
R
Shraiman
Boris I
BI
Alon
Uri
U
D000465:Algorithms; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D007700:Kinetics; D009876:Operon; D011401:Promoter Regions, Genetic; D013014:SOS Response, Genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000099160:LexA Repressor Protein
D001426:Bacterial Proteins; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein