Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences

By measuring individual mRNA production at the single-cell level, we investigated the lac promoter’s transcriptional transition during cell growth phases. In exponential phase, variation in transition rates generates two mixed phenotypes, low and high numbers of mRNAs, by modulating their burst frequency and sizes. Independent activation of the regulatory-gene sequence does not produce bimodal populations at the mRNA level, but bimodal populations are produced when the regulatory gene is activated coordinately with the upstream and downstream region promoter sequence (URS and DRS, respectively). Time-lapse microscopy of mRNAs for lac and a variant lac promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between the URS and the DRS in transcriptional regulation determines population diversity.