TY - JOUR T1 - Transcriptional Regulation: Effects of Promoter Proximal Pausing on Speed, Synchrony and Reliability A1 - Boettiger, Alistair N. A1 - Ralph, Peter L. A1 - Evans, Steven N. Y1 - 2011/05/12 N2 - Author Summary Gene activation is an inherently random process because numerous diffusing proteins and DNA must first interact by random association before transcription can begin. For many genes the necessary protein–DNA associations only begin after activation, but it has recently been noted that a large class of genes in multicellular organisms can assemble the initiation complex of proteins on the core promoter prior to activation. For these genes, activation merely releases polymerase from the preassembled complex to transcribe the gene. It has been proposed on the basis of experiments that such a mechanism, while possibly costly, increases both the speed and the synchrony of the process of gene transcription. We study a realistic model of gene transcription, and show that this conclusion holds for all but a tiny fraction of the space of physical rate parameters that govern the process. The improved control of cell-to-cell variations afforded by regulation through a paused polymerase may help multicellular organisms achieve the high degree of coordination required for development. Our approach has also generated tools with which one can study the effects of analogous changes in other molecular networks and determine the relative importance of various molecular binding rates to particular system properties. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 7 IS - 5 UR - https://doi.org/10.1371/journal.pcbi.1001136 SP - e1001136 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1001136 ER -