Gene syntax defines supercoiling-mediated transcriptional feedback
Name
Gene syntax defines supercoiling-mediated transcriptional feedback.pdf
Description
Accepted version
Size
10.81 MB
Format
Adobe PDF
Checksum (MD5)
393f7816c7693b6f98adbb55e08191b1
Author(s)
Johnstone, Christopher P
Love, Kasey S
Kabaria, Sneha R
Jones, Ross D
Blanch-Asensio, Albert
Ploessl, Deon S
Peterman, Emma L
Lee, Rachel
Yun, Jiyoung
Oakes, Conrad G
Date Issued
April 30, 2026
Journal
Science
Publisher
American Association for the Advancement of Science
Citation
Christopher P. Johnstone et al. , Gene syntax defines supercoiling-mediated transcriptional feedback. Science 392, eadw1925 (2026).
Version
Author's final manuscript
Abstract
Gene syntax—the order and arrangement of genes and their regulatory elements—shapes the dynamic coordination of both natural and synthetic gene circuits. Transcription at one locus perturbs the transcription of adjacent genes, but the molecular basis of this effect remains poorly understood. In this work, we show that supercoiling-mediated feedback arises from transcription and regulates expression of adjacent genes in a syntax-specific manner. Using a suite of assays, we measured syntax- and induction-dependent formation of chromatin structures in human induced pluripotent stem cells. Applying syntax as a design parameter, we built and improved compact gene circuits, tuning the expression mean, noise, and stoichiometry across delivery methods and cell types. Integrating supercoiling mediated feedback into models of gene regulation will expand our understanding of native and synthetic systems.
Terms of Use
Creative Commons Attribution-NonCommercial-ShareAlike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/science.adw1925
