A Mechanochemical Model of Transcriptional Bursting*

Variability in gene expression ensures that cells with the same genotype always exhibit different phenotypes. Transcription bursting, or the random interruptions in the production of messenger RNA molecules, is one probable cause of this ubiquitous variability. Yet, the molecular mechanisms behind the bursting behavior remain unclear. Recent studies suggest that DNA supercoiling, which occurs during transcription, might be directly related to the bursting behavior. Stimulated by these observations, we developed a stochastic mechano-chemical model of supercoiling-induced transcriptional bursting. Using thermodynamically consistent coupling between mechanical and chemical processes, dynamic properties of transcription are explicitly evaluated. Theoretical analysis shows that the transcription bursting is observed when both supercoiling and the mechanical stress-release due to an enzyme gyrase are present in the system. A comparison with experimental data on bacteria allowed us to evaluate the energetic cost of supercoiling during transcription. We find that a relatively weak mechano-chemical coupling allows transcription to be regulated most effectively.