G-quadruplex structures affect the immune response to bacterial infection in mouse macrophages.

Authors

Philipp Schult, Melanie Kastl, Jennifer Szlapa, Konstantinos Symeonidis, Salie Maasewerd, Bernardo Franklin, Alea Radcke, Stefan A Juranek, Zeinab Abdullah, Katrin Paeschke

Published in

Nature communications. Volume 17. Issue 1. Oct 20, 2026. Epub Oct 20, 2026.

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.

PMID:
42901949
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

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