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

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.

Main text: 9 pages, 4 figures. Supporting Information Text: 12 pages, 11 figures

References in corpus (5)

• Geometry of Calugareanu's theorem
• Bend-Induced Twist Waves and the Structure of Nucleosomal DNA
• On the Tree-Like Structure of Rings in Dense Solutions
• Mechanical Properties of Transcription
• Dynamical Scaling and Phase Coexistence in Topologically-Constrained DNA Melting

Cited by in corpus (7)

• DNA supercoiling in bacteria: state of play and challenges from a viewpoint of physics based modeling
• Equilibrium Fluctuations of DNA Plectonemes
• Transcribing RNA polymerases: Dynamics of Twin Supercoiled Domains
• Large bubble drives melting in circular DNA
• Twin Supercoil Domain couples the dynamics of molecular motors and plectonemes during bacterial DNA transcription and replication
• Topological digestion drives time-varying rheology of entangled DNA fluids
• DNA geometry around highly transcribed bacterial genes