Supercoiling-mediated feedback rapidly couples and tunes transcription
Name
1-s2.0-S2211124722013420-main.pdf
Description
Published version
Size
2.75 MB
Format
Adobe PDF
Checksum (MD5)
5222360881da1b8dc1ac503d2fdb22b3
Author(s)
Johnstone, Christopher P
Galloway, Kate E
Date Issued
October 2022
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Johnstone, Christopher P and Galloway, Kate E. 2022. "Supercoiling-mediated feedback rapidly couples and tunes transcription." Cell Reports, 41 (3).
Version
Final published version
Abstract
Transcription induces a wave of DNA supercoiling, altering the binding affinity of RNA polymerases and reshaping the biochemical landscape of gene regulation. As supercoiling rapidly diffuses, transcription dynamically reshapes the regulation of proximal genes, forming a complex feedback loop. However, a theoretical framework is needed to integrate biophysical regulation with biochemical transcriptional regulation. To investigate the role of supercoiling-mediated feedback within multi-gene systems, we model transcriptional regulation under the influence of supercoiling-mediated polymerase dynamics, allowing us to identify patterns of expression that result from physical inter-gene coupling. We find that gene syntax-the relative ordering and orientation of genes-defines the expression profiles, variance, burst dynamics, and inter-gene correlation of two-gene systems. Furthermore, supercoiling can enhance or weaken biochemical regulation. Our results suggest that supercoiling couples behavior between neighboring genes, providing a regulatory mechanism that tunes transcriptional variance in engineered gene networks and explains the behavior of co-localized native circuits.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2022.111492
