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

• Published in: PLoS computational biology Vol. 18; no. 9; p. e1009788
• Main Authors: Geng, Yuncong, Bohrer, Christopher Herrick, Yehya, Nicolás, Hendrix, Hunter, Shachaf, Lior, Liu, Jian, Xiao, Jie, Roberts, Elijah
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.09.2022; Public Library of Science (PLoS)
• Subjects: Binding sites; Biology and life sciences; Cooperation; Deoxyribonucleic acid; Diffusion rate; DNA; DNA-directed RNA polymerase; DNA-Directed RNA Polymerases - metabolism; Domains; E coli; Elongation; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Gene expression; Gene Expression Regulation, Bacterial - genetics; Gene regulation; Genes; Genetic aspects; Genetic regulation; Genetic transcription; Genomes; Learning models (Stochastic processes); Medicine and Health Sciences; Physical Sciences; Proteins; Research and Analysis Methods; RNA polymerase; RNA polymerases; Stochastic models; Stochasticity; Structure; Supercoiling; Topology; Transcription; Transcription, Genetic - genetics; Translocation; United States
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1009788

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 developed a spatially resolved supercoiling model of transcription. The integrated model describes how RNAP activity feeds back with the local DNA supercoiling and how this mechanochemical feedback controls transcription, subject to topoisomerase activities and stochastic topological domain formation. This model establishes that transcription-induced supercoiling mediates the cooperation of co-transcribing RNAP molecules in highly expressed genes, and this cooperation is achieved under moderate supercoiling diffusion and high topoisomerase unbinding rates. It predicts that a topological domain could serve as a transcription regulator, generating substantial transcriptional noise. It also shows the relative orientation of two closely arranged genes plays an important role in regulating their transcription. The model provides a quantitative platform for investigating how genome organization impacts transcription.