Supercoiling-mediated feedback rapidly couples and tunes transcription

Area of Science:

• Biophysics
• Molecular Biology
• Systems Biology

Background:

• Transcription generates DNA supercoiling, which affects RNA polymerase binding and gene regulation.
• Supercoiling dynamics create feedback loops influencing proximal gene expression.
• A theoretical framework is needed to link biophysical and biochemical gene regulation.

Purpose of the Study:

• To model transcriptional regulation considering supercoiling-mediated polymerase dynamics in multi-gene systems.
• To investigate how physical inter-gene coupling via supercoiling affects gene expression patterns.
• To understand the role of supercoiling-mediated feedback in gene networks.

Main Methods:

• Computational modeling of transcriptional regulation.
• Analysis of supercoiling-mediated polymerase dynamics.
• Investigation of gene syntax effects on expression profiles.

Main Results:

• Gene syntax (ordering and orientation) significantly impacts expression profiles, variance, burst dynamics, and inter-gene correlations in two-gene systems.
• Supercoiling can modulate the strength of biochemical regulatory mechanisms.
• Supercoiling creates physical coupling between neighboring genes, influencing their regulatory behavior.

Conclusions:

• Supercoiling acts as a physical coupling mechanism between adjacent genes, tuning transcriptional variance in engineered networks.
• This physical coupling explains the behavior of co-localized native gene circuits.
• Understanding supercoiling-mediated feedback is crucial for designing synthetic gene networks.