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

Mahendra Kumar Prajapat, Andre S. Ribeiro

    Research output: Contribution to journalArticleScientificpeer-review

    3 Citations (Scopus)
    7 Downloads (Pure)

    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.

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

    Keywords

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

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • General

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