An analytically tractable framework for transcription-extrusion coupling in chromatin loop formation

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.