TUTCRIS - Tampereen teknillinen yliopisto


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

Tutkimustuotos: Konferenssiesitys, posteri tai abstrakti


TilaJulkaistu - 7 joulukuuta 2017


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.