Gene syntax defines supercoiling-mediated transcriptional feedback
Summary
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-
Content
# Gene syntax defines supercoiling-mediated transcriptional feedback
*Published: 2026 Apr 30*
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.
DOI: 10.1126/science.adw1925