Dynamic DNA structure controls memory formation by switching genes on and off. A specific DNA shape, G-quadruplex (G4-DNA), builds up in neurons during learning and regulates memory-related gene activity. Adjusting this structure alters memory formation, highlighting a new molecular mechanism underpinning brain plasticity and cognitive health.
April 2024 – The Journal of Neuroscience
Key takeaways
- DNA shape regulates memory genes: G4-DNA, a four-stranded DNA structure, forms dynamically in neurons during learning experiences and is essential for switching memory-related genes on and off. This finding highlights how shifts in DNA structure—not just sequence—can drive cognitive processes and adaptive behaviour linked to memory and learning
- Helicase DHX36 controls G4-DNA function: The enzyme DHX36 is crucial for resolving G4-DNA structures after they form. Its activity ensures proper timing of gene activation. When DHX36 is reduced, G4-DNA accumulates in neurons, leading to impaired memory consolidation and altered expression of key genes involved in neuroplasticity
- Fear extinction memory depends on G4-DNA: The formation and resolution of G4-DNA in the medial prefrontal cortex are vital for fear extinction learning. Targeting this DNA shape with precision tools disrupted the ability to form long-lasting extinction memories, revealing a core role for G4-DNA in adaptive emotional responses
- G4-DNA links to brain ageing pathways: Many genes regulated by G4-DNA are involved in synaptic function, ion channel signalling and RNA processing—pathways commonly associated with age-related cognitive decline. This suggests that maintaining proper G4-DNA dynamics could be a novel strategy for preserving memory and cognitive health across the lifespan
Read the article at: Marshall, Paul R., et al. “DNA G-Quadruplex Is a Transcriptional Control Device That Regulates Memory.” The Journal of Neuroscience, vol. 44, no. 15, 2024, https://doi.org/10.1523/JNEUROSCI.0093-23.2024.
