The Generation of Promoter-Mediated Transcriptional Noise in Bacteria

Namiko Mitarai, Ian B Dodd, Michael T Crooks and Kim Sneppen

PLOS Computational Biology, 2008, vol. 4, issue 7, 1-9

Abstract: Noise in the expression of a gene produces fluctuations in the concentration of the gene product. These fluctuations can interfere with optimal function or can be exploited to generate beneficial diversity between cells; gene expression noise is therefore expected to be subject to evolutionary pressure. Shifts between modes of high and low rates of transcription initiation at a promoter appear to contribute to this noise both in eukaryotes and prokaryotes. However, models invoked for eukaryotic promoter noise such as stable activation scaffolds or persistent nucleosome alterations seem unlikely to apply to prokaryotic promoters. We consider the relative importance of the steps required for transcription initiation. The 3-step transcription initiation model of McClure is extended into a mathematical model that can be used to predict consequences of additional promoter properties. We show in principle that the transcriptional bursting observed at an E. coli promoter by Golding et al. (2005) can be explained by stimulation of initiation by the negative supercoiling behind a transcribing RNA polymerase (RNAP) or by the formation of moribund or dead-end RNAP-promoter complexes. Both mechanisms are tunable by the alteration of promoter kinetics and therefore allow the optimization of promoter mediated noise.Author Summary: Noise in gene expression is important for phenotypic variation among genetically identical cells. The gene expression will be particularly sensitive to noise in transcription initiation. Transcription initiation from a given promoter involves multiple steps, each of which could be rate limiting. In this paper we discuss how transcription initiation could come in bursts, separated by long periods where the promoter is inactive. Our results are compared to recent data of Golding et al. (2005), which suggest that transcriptions from some prokaryotic promoters occur in a highly irregular burst-like fashion. We show that the observed bursting could be caused by one of two alternate mechanisms. One possibility is that changes in supercoiling induced by previous RNA polymerase can help a subsequent RNAP to enter directly into open complex. Another possibility is that an RNAP at the promoter sometimes forms a dead-end complex, and thereby occludes the promoter for a sizeable amount of time.

Date: 2008
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1000109

DOI: 10.1371/journal.pcbi.1000109

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