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Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
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The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
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Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter? 
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An analytically tractable framework for transcription-extrusion coupling in chromatin loop formation.

Leiyan Chen1, Zhenquan Zhang2, Zihao Wang1

  • 1School of Mathematics, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China; Guangdong Province Key Laboratory of Computational Science, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China.

Journal of Theoretical Biology
|April 18, 2026
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Transcription by RNA polymerase (RNAP) disrupts chromatin loop extrusion. Our model shows increased RNAP density suppresses full extrusion, favoring stripe formation, impacting 3D genome folding.

Keywords:
ChromatinGene regulationLoop extrusionStochastic modelling

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Area of Science:

  • Molecular Biology
  • Genomics
  • Biophysics

Background:

  • Chromatin loop extrusion is key to 3D genome folding.
  • Transcription by RNA polymerase (RNAP) interferes with this process.
  • A quantitative model for this interference is lacking.

Purpose of the Study:

  • To develop a quantitative model for transcription-extrusion interference.
  • To assess how RNAP density and gene length affect chromatin organization.
  • To explain experimental observations of Hi-C patterns in transcribed regions.

Main Methods:

  • Developed a stochastic process model on a 1D lattice.
  • Incorporated RNAPs as direction-dependent, permeable moving barriers.
  • Utilized stochastic resetting and first-passage theory.

Main Results:

  • RNAP slows cohesin translocation and creates asymmetric impediments.
  • Increased RNAP density suppresses full extrusion (corner peaks) and enhances stripe occurrence.
  • Model predicts a threshold transition and amplification of trends for longer genes.

Conclusions:

  • RNAP density quantitatively shapes chromatin organization by modulating loop extrusion.
  • The model provides a mechanistic explanation for Hi-C stripe and corner-peak patterns.
  • This framework advances understanding of genome folding in transcriptionally active regions.