DNA G-quadruplex is a transcriptional control device that regulates memory

Paul Robert Marshall; Joshua Davies; Qiongyi Zhao; Wei‐Siang Liau; Yujin Lee; Dean Basic; Ambika Periyakaruppiah; Esmi Lau Zajaczkowski; Laura Jane Leighton; Sachithrani U. Madugalle; Mason R. B. Musgrove; Marcin Kielar; Arie Maeve Brueckner; Hao Gong; Haobin Ren; Alexander Walsh; Lech Kaczmarczyk; Walker S. Jackson; Alon Chen; Robert C. Spitale; Timothy William Bredy

doi:10.1523/jneurosci.0093-23.2024

NeuroscienceJournal of NeuroscienceFeb 28, 2024

Peer-reviewed journal article

DNA G-quadruplex is a transcriptional control device that regulates memory

Paul Robert Marshall iD, Joshua Davies iD, Qiongyi Zhao iD, Wei‐Siang Liau iD, Yujin Lee iD, Dean Basic iD, Ambika Periyakaruppiah, Esmi Lau Zajaczkowski iD, Laura Jane Leighton iD, Sachithrani U. Madugalle iD, Mason R. B. Musgrove iD, Marcin Kielar iD, Arie Maeve Brueckner, Hao Gong iD, Haobin Ren iD, Alexander Walsh, Lech Kaczmarczyk iD, Walker S. Jackson iD, Alon Chen iD, Robert C. Spitale iD, Timothy William Bredy iD

Abstract

The conformational state of DNA fine-tunes the transcriptional rate and abundance of RNA. Here we report that DNA G-quadruplex (G4-DNA) accumulates in neurons in an experience-dependent manner, and that this is required for the transient silencing and activation of genes that are critically involved in learning and memory. In addition, site-specific resolution of G4-DNA by dCas9-mediated deposition of the helicase DHX36 impairs fear extinction memory. Dynamic DNA structure states therefore represent a key molecular mechanism underlying memory consolidation. One-Sentence SummaryG4-DNA is a molecular switch that enables the temporal regulation of the gene expression underlying the formation of fear extinction memory.

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