# Transcription-driven DNA Supercoiling: Non-Equilibrium Dynamics and Action-at-a-distance

## TL;DR

This study uses simulations to reveal how transcription causes asymmetric DNA supercoiling and influences DNA-protein interactions at a distance, challenging traditional symmetric models.

## Contribution

It introduces a detailed simulation framework showing asymmetric supercoiling domains and action-at-a-distance effects of transcription on DNA structure.

## Key findings

- Supercoiling domains are asymmetric, with plectonemes forming far from RNAP.
- Positive supercoils destabilize nucleosomes before RNAP reaches them.
- Twist diffusion is fast, while writhe relaxation is slow and multi-step.

## Abstract

We study the effect of transcription on the kinetics of DNA supercoiling in 3D by means of Brownian dynamics simulations of a single nucleotide resolution coarse-grained model for double stranded DNA. By accounting for the action of a transcribing RNA polymerase (RNAP), we characterise the geometry and non equilibrium dynamics of the twin supercoiling domains forming on each side of the RNAP. Textbook pictures depict such domains as symmetric, with plectonemes (writhed DNA) appearing close to the RNAP. On the contrary, we find that the twist generated by transcription results in asymmetric domains, with plectonemes formed far from the RNAP. We show that this translates into an "action-at-a-distance" on DNA-binding proteins: for instance, positive supercoils downstream of an elongating RNAP destabilise nucleosomes long before the transcriptional machinery reaches the histone octamer. To understand these observations we use our framework to quantitatively analyse the relaxation dynamics of supercoiled DNA. We find a striking separation of timescales between twist diffusion, which is a simple and fast process, and writhe relaxation, which is slow and entails multiple steps.