A promoter G-quadruplex recruits Hrb27C to regulate NEMO and immune defense against Lyme disease pathogens in the deer tick.

A promoter G-quadruplex in the NEMO gene of Ixodes scapularis is essential for NEMO transcription and influences Lyme disease pathogen burden.

• Why it matters: Understanding how noncanonical DNA structures regulate immune responses in arthropods can reveal mechanisms of host-pathogen interactions and potential targets for controlling disease transmission.
• What they did: The study used circular dichroism, spectroscopy, and fluorescence assays to show a stable G4 structure in the NEMO promoter, and luciferase assays to demonstrate its necessity for NEMO expression, with disruption reducing NEMO levels and increasing Borrelia burgdorferi burden.
• The result: Disruption of the G4 decreased NEMO expression and increased pathogen load, while the protein Hrb27C was identified as a specific G4 binder that promotes NEMO transcription, linking DNA topology to tick immune defense.