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Added value of autoregulation and multi-step kinetics of transcription initiation

Research output: Contribution to journalArticleScientificpeer-review

Details

Original languageEnglish
Article number181170
JournalRoyal Society Open Science
Volume5
Issue number11
DOIs
Publication statusPublished - 1 Nov 2018
Publication typeA1 Journal article-refereed

Abstract

Bacterial gene expression regulation occurs mostly during transcription, which has two main rate-limiting steps: the close complex formation, when the RNA polymerase binds to an active promoter, and the subsequent open complex formation, after which it follows elongation. Tuning these steps’ kinetics by the action of e.g. transcription factors, allows for a wide diversity of dynamics. For example, adding autoregulation generates single-gene circuits able to perform more complex tasks. Using stochastic models of transcription kinetics with empirically validated parameter values, we investigate how autoregulation and the multi-step transcription initiation kinetics of single-gene autoregulated circuits can be combined to fine-tune steady state mean and cell-to-cell variability in protein expression levels, as well as response times. Next, we investigate how they can be jointly tuned to control complex behaviours, namely, time counting, switching dynamics and memory storage. Overall, our finding suggests that, in bacteria, jointly regulating a single-gene circuit’s topology and the transcription initiation multi-step dynamics allows enhancing complex task performance.

ASJC Scopus subject areas

Keywords

  • Autoregulation mechanisms, Cell-to-cell variability, Rate-limiting steps, Transcription initiation

Publication forum classification

Field of science, Statistics Finland