A Biophysical Model of Supercoiling Dependent Transcription Predicts a Structural Aspect to Gene Regulation

Abstract

Background: Transcription in Escherichia coli generates positive supercoiling in the DNA, which is relieved by the enzymatic activity of gyrase. Recently published experimental evidence suggests that transcription initiation and elongation are inhibited by the buildup of positive supercoiling. It has therefore been proposed that intermittent binding of gyrase plays a role in transcriptional bursting. Considering that transcription is one of the most fundamental cellular processes, it is desirable to be able to account for the buildup and release of positive supercoiling in models of transcription. Results: Here we present a detailed biophysical model of gene expression that incorporates the effects of supercoiling due to transcription. By directly linking the amount of positive supercoiling to the rate of transcription, the model predicts that highly transcribed genes' mRNA distributions should substantially deviate from Poisson distributions, with enhanced density at low mRNA copy numbers. Additionally, the model predicts a high degree of correlation between expression levels of genes inside the same supercoiling domain. Conclusions: Our model, incorporating the supercoiling state of the gene, makes specific predictions that differ from previous models of gene expression. Genes in the same supercoiling domain influence the expression level of neighboring genes. Such structurally dependent regulation predicts correlations between genes in the same supercoiling domain. The topology of the chromosome therefore creates a higher level of gene regulation, which has broad implications for understanding the evolution and organization of bacterial genomes.

Likelihood for transcriptions in a genetic regulatory system under asymmetric stable Lévy noise

“…This intermittent manner [31,32,33,34] resembles the features of a stable Lévy motion, which is a non-Gaussian process with jumps.…”

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

“…The relationship between DNA topology and gene expression is not unidirectional: transcription itself creates topological change in the DNA template, so environmental factors that influence transcription initiation, elongation or termination all have the potential to modulate the superhelicity of the DNA in the genome (Bohrer and Roberts 2016;Kouzine et al 2008;Kotlajich et al 2015;Ma and Wang 2014a).…”

Bacterial genome architecture shapes global transcriptional regulation by DNA supercoiling

“…Several TSC models have been recently proposed [15,19,16,17] in a biophysical and essentially theoretical perspective, e.g., aiming at reproducing so-called "transcription bursts" [20]. But strikingly, no attempt has been made so far to simulate any specific experimental system, for which these models lack important components (e.g., explicit topoisomerase enzymes).…”