DNA Supercoiling Drives a Transition between Collective Modes of Gene Synthesis

TL;DR

This paper presents a continuum model showing how DNA supercoiling influences the collective behavior of RNA polymerases, explaining the transition between efficient gene transcription and repression.

Contribution

It introduces a novel deterministic model linking DNA supercoiling and RNAP density to transcription modes, capturing experimentally observed dynamics.

Findings

Two distinct transcription modes driven by supercoiling: fluid and torsionally stressed.

Model quantitatively matches experimental observations of RNAP dynamics.

Promoter activity controls the transition between cooperative and antagonistic RNAP behavior.

Abstract

Recent experiments showed that multiple copies of the molecular machine RNA polymerase (RNAP) can efficiently synthesize mRNA collectively in the active state of the promoter. However, environmentally-induced promoter repression results in long-distance antagonistic interactions that drastically reduce the speed of RNAPs and cause a quick arrest of mRNA synthesis. The mechanism underlying this transition between cooperative and antagonistic dynamics remains poorly understood. In this Letter, we introduce a continuum deterministic model for the translocation of RNAPs, where the speed of an RNAP is coupled to the local DNA supercoiling as well as the density of RNAPs on the gene. We assume that torsional stress experienced by individual RNAPs is exacerbated by high RNAP density on the gene and that transcription factors act as physical barriers to the diffusion of DNA supercoils. We show that this minimal model exhibits two transcription modes mediated by the torsional stress: a fluid mode when the promoter is active and a torsionally stressed mode when the promoter is repressed, in quantitative agreement with experimentally observed dynamics of co-transcribing RNAPs. Our work provides an important step towards understanding the collective dynamics of molecular machines involved in gene expression.