G-quadruplex structures affect the immune response to bacterial infection in mouse macrophages
Abstract
Macrophages orchestrate immunity via transcriptional reprogramming, largely controlled by the master regulator NF-κB. However, mechanisms of promoter selection remain enigmatic. Here, we reveal that DNA secondary structures called G-quadruplexes (G4s) modulate the macrophage transcriptome during inflammation. By investigating the G4 ligand pyridostatin (PDS) in lipopolysaccharide-stimulated macrophages, we establish that G4 stabilization significantly decreases the inflammatory response without affecting mitochondrial metabolism or pathogen clearance. Instead, NF-κB-dependent transcription of activation markers and proinflammatory cytokines is selectively repressed. Using chromatin accessibility profiling, NF-κB ChIP, and in silico predictions, we demonstrate that G4 stabilization sterically hinders NF-κB promoter occupancy. Furthermore, PDS stabilizes transient, transcription-induced G4s, prematurely shutting down transcription and reverting local chromatin to a dormant state. Thus, G4 formation represents a potential strategy to modulate dysregulated macrophage activation.
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BibTeX
@article{schult2026gquadruplex,
title = {{G-quadruplex structures affect the immune response to bacterial infection in mouse macrophages}},
author = {Philipp Schult and Melanie Kastl and Jennifer Szlapa and Konstantinos Symeonidis and Salie Maasewerd and Bernardo Franklin and Alea Radcke and Stefan A. Juranek and Zeinab Abdullah and Katrin Paeschke},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78610-w},
url = {https://www.nature.com/articles/s41467-026-78610-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - G-quadruplex structures affect the immune response to bacterial infection in mouse macrophages
AU - Philipp Schult
AU - Melanie Kastl
AU - Jennifer Szlapa
AU - Konstantinos Symeonidis
AU - Salie Maasewerd
AU - Bernardo Franklin
AU - Alea Radcke
AU - Stefan A. Juranek
AU - Zeinab Abdullah
AU - Katrin Paeschke
PY - 2026
DA - 2026/10/20
JO - Nature Communications
DO - 10.1038/s41467-026-78610-w
UR - https://www.nature.com/articles/s41467-026-78610-w
AB - Macrophages orchestrate immunity via transcriptional reprogramming, largely controlled by the master regulator NF-κB. However, mechanisms of promoter selection remain enigmatic. Here, we reveal that DNA secondary structures called G-quadruplexes (G4s) modulate the macrophage transcriptome during inflammation. By investigating the G4 ligand pyridostatin (PDS) in lipopolysaccharide-stimulated macrophages, we establish that G4 stabilization significantly decreases the inflammatory response without affecting mitochondrial metabolism or pathogen clearance. Instead, NF-κB-dependent transcription of activation markers and proinflammatory cytokines is selectively repressed. Using chromatin accessibility profiling, NF-κB ChIP, and in silico predictions, we demonstrate that G4 stabilization sterically hinders NF-κB promoter occupancy. Furthermore, PDS stabilizes transient, transcription-induced G4s, prematurely shutting down transcription and reverting local chromatin to a dormant state. Thus, G4 formation represents a potential strategy to modulate dysregulated macrophage activation.
SN - 2041-1723
ER -