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TORCphysics: a physical model of DNA-topology-controlled gene expression.

Victor Velasco-Berrelleza1, Penn Faulkner Rainford2, Aalap Mogre3

  • 1School of Mathematical and Physical Sciences, University of Sheffield, Hounsfield Road, Sheffield, S3 7RH, United Kingdom.

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Summary

This study introduces TORCphysics, a model simulating DNA supercoiling

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Area of Science:

  • * Molecular Biology
  • * Biophysics
  • * Computational Biology

Background:

  • * DNA superhelicity and transcription are intrinsically linked, with topological changes affecting gene expression and vice versa.
  • * Gene expression can modulate local DNA torsional stress, influencing neighboring gene activity.
  • * Understanding these complex regulatory mechanisms is crucial for deciphering gene control.

Purpose of the Study:

  • * To introduce a novel one-dimensional physical model, TORCphysics, for simulating supercoiling-mediated gene regulation.
  • * To provide a flexible computational framework for analyzing gene circuit dynamics.
  • * To deepen the comprehension of gene regulation mechanisms influenced by DNA topology.

Main Methods:

  • * Development of the TORCphysics model, a 1D physical simulation.
  • * Input: Genome architecture (plasmid or chromosomal DNA) with constrained ends under specific biological conditions.
  • * Output: Simulation of DNA supercoiling and its effect on gene expression.

Main Results:

  • * Gene expression profiles are significantly influenced by gene circuit design parameters.
  • * Key factors include gene location, topological barriers, promoter sequences, and topoisomerase activity.
  • * The model demonstrates the direct impact of DNA topology on gene expression patterns.

Conclusions:

  • * TORCphysics offers a versatile platform for simulating gene circuits with customizable protein activity models.
  • * The model facilitates a deeper understanding of how DNA supercoiling regulates gene expression.
  • * This research establishes a flexible framework for physical simulations in gene regulation studies.