A spatially resolved stochastic model reveals the role of supercoiling in transcription regulation

Abstract

In Escherichia coli, translocation of RNA polymerase (RNAP) during transcription introduces supercoiling to DNA, which influences the initiation and elongation behaviors of RNAP. To quantify the role of supercoiling in transcription regulation, we develop a spatially resolved supercoiling model of transcription, describing RNAP-supercoiling interactions, topoisomerase activities, stochastic topological domain formation, and supercoiling diffusion in all transcription stages. This model establishes that transcription-induced supercoiling mediates the cooperation of co-transcribing RNAP molecules in highly expressed genes. It reveals that supercoiling transmits RNAP-accessible information through DNA and enables different RNAP molecules to communicate within and between genes. It thus predicts that a topological domain could serve as a transcription regulator, generating substantial transcription bursting and coordinating communications between adjacent genes in the domain. The model provides a quantitative platform for further theoretical and experimental investigations of how genome organization impacts transcription.

VariableDNAtopology is an epigenetic generator of physiological heterogeneity in bacterial populations

“…In bacteria, interference with RNA polymerase translocation by supercoil accumulation contributes to what has been termed transcription "bursts" (Figure 1). Bursting refers to the stochas- (Ancona et al, 2019;Chong et al, 2014;Geng et al, 2022;Klindziuk & Kolomeisky, 2021). Supercoil diffusion will not be possible if the DNA is not free to rotate, so the intervention of gyrase is essential.…”

“…The introduction of DNA gyrase overcomes the interference with transcription elongation. The data indicate that over‐twisting of the DNA in front of an elongation complex inhibits further transcription of the affected gene until either DNA gyrase removes the obstruction or the supercoils diffuse away from the site by DNA rotation (Ancona et al, 2019; Chong et al, 2014; Geng et al, 2022; Klindziuk & Kolomeisky, 2021). Supercoil diffusion will not be possible if the DNA is not free to rotate, so the intervention of gyrase is essential.…”

“…These DNA topological changes are both the causes of, and the consequences of, shifts in the expression of the transcriptome (Dorman, 2019). They are a manifestation of the combined actions of the topoisomerases that manage the DNA topological shifts and of the altered activities of RNA polymerase at hundreds of transcription units (Cameron et al, 2017; Geng et al, 2022; Kim et al, 2019; Stracy et al, 2019). In addition to the task of expressing genetic information, transcription also sets the 3D architecture of the nucleoid (Badrinarayanan et al, 2015; Cagliero et al, 2013; Jeong et al, 2004; Le & Laub, 2016; Shen & Landick, 2019).…”

Emergence of Supercoiling-Mediated Regulatory Networks through the Evolution of Bacterial Chromosome Organization

“…Multiple modeling works have recently addressed the simulation of the transcription-supercoiling coupling, reporting contrasted results (El Houdaigui et al, 2019;Geng et al, 2022;Sevier and Hormoz, 2022;Johnstone and Galloway, 2022;Boulas et al, 2023). Quantitative regulatory rules that result from this coupling thus still remain to be fully characterized.…”