Elucidating the Influence of Chromosomal Architecture on Transcriptional Regulation in Prokaryotes – Observing Strong Local Effects of Nucleoid Structure on Gene Regulation

Abstract

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Both intrinsic and extrinsic mechanisms regulating bacterial expression have been elucidated and described, however, such studies have mainly focused on local effects on the two-dimensional structure of the prokaryote genome while long-range as well as spatial interactions influencing gene expression are still only poorly understood. In this paper, we investigate the association between co-expression and distance between genes, using RNA-seq data at multiple growth phases in order to illuminate whether such conserved patterns are an indication of a gene regulatory mechanism relevant for prokaryotic cell proliferation, adaption, and evolution. We observe recurrent sinusoidal patterns in correlation of pairwise expression as function of genomic distance and rule out that these are caused by transcription-induced supercoiling gradients, gene clustering in operons, or association with regulatory transcription factors (TFs). By comparing spatial proximity for pairs of genomic bins with their correlation of pairwise expression, we further observe a high co-expression proportional with the spatial proximity. Based on these observations, we propose that the observed patterns are related to nucleoid structure as a product of transcriptional spilling, where genes actively influence transcription of spatially proximal genes through increases within shared local pools of RNA polymerases (RNAP), and actively spilling transcription onto neighboring genes.

Keywords

• bacterial nucleoid
• gene co-expression
• chromosomal architecture
• transcriptional spilling
• predicting supercoils