On the interaction of DNA replication and transcriptional regulation

Abstract

DNA replication introduces a gradient of gene copy numbers, and in Bacteria it affects gene expression accordingly. In E. coli and other species, the slope of the gradient averaged over the population can be predicted on the basis of its relationship with growth rate. In this work we integrated this growth- and position-dependent gradient into a classical transcriptional regulation model, to highlight their interaction. The theoretical treatment of our model highlights that the sensitivity to transcription factor-mediated regulations acquires an additional dimension related to the position of a locus on the oriter axis and to division time. This reinforces the idea of replication as an additional layer in gene regulation. We highlight here that replication- and transcription factor-mediated regulations can in theory work in concert or counteract each other, and we discuss why this is important from an evolutionary point of view with respect to both steady state transcript abundance and its variance across conditions. Finally, we note that this treatment may improve the estimation of kinetic parameters for transcription factor activity using RNA-seq data, and the estimation of the dispersion factor in differential gene expression analysis when division time across conditions changes significantly.