Promoters Initiation Kinetics Affect the Influence of Component Genes Dynamics on Gene Networks Behavior

Complex bioprocesses, such as cell growth and replication, are made possible by the temporally orderly execution of simpler semi-independent processes, such as time counting and decision making, that occur at various spatial and temporal scales. Understanding the information flow between the various scales is a fundamental goal of life sciences. It is well established that, in Escherichia coli, transcription is a multi-step process [1,2] whose regulation occurs mostly during the initial, rate-limiting steps via the action of activators, repressors and global regulatory molecules [3-5]. This results in a specific RNA production dynamics that defines also protein numbers. Recent studies [6-9] started exploring how the ratelimiting
steps of individual genes affect genetic circuits. Here we present our recent findings on this subject, obtained from a comparison of the inner-dynamics of transcription when inducing the same promoter, Plac/ara-1 by different
inducers (IPTG and arabinose) and different promoters (Plac/ara-1 and Plac). This comparison is based on data from a recent measurement technique of the duration of the steps prior and after initiation of the open complex [5][6] from measurements of time-intervals between consecutive RNA production events in single cells by live time-lapse microscopy and MS2-GFP RNA tagging. Next, using stochastic models of 2-genes switches with realistic multi-step initiation kinetics and empirically validated parameter values, we explore how rate-limiting steps in initiation can tune noise propagation and a circuit’s responsiveness to external signals.