On the interaction of DNA replication and transcriptional regulation

DNA replication introduces a gradient of gene copy number, and in Bacteria it affects gene expression accordingly. In E. coli and other species, the average gradient in the population can be estimated on the basis of a relationship with the growth rate. In this work we integrated this growth- and position-dependent gradient into a classical transcriptional regulation model, to evaluate their interactions. The theoretical treatment of our model highlights that the sensitivity to transcription factor-mediated regulations acquires and extra-dimension related to the position of a locus on the ori/ter axis and division time. This reinforce the idea of replication as an additional layer of complexity in gene regulation. We highlight that the contributions of the replication- and transcription factor-mediated regulations to the final variance of the target gene can in theory work in concert or counteract each other, and we discuss why this is important from an evolutionary point of view. Finally, we highlight the fact that this treatment may improve the estimation of kinetic parameters for transcription factor activity using RNA-seq data, and the estimation of transcript variance in differential gene expression analysis. ### Competing Interest Statement The authors have declared no competing interest.