DNA G-Quadruplex Is a Transcriptional Control Device That Regulates Memory

The conformational state of DNA fine-tunes the transcriptional rate and abundance of RNA. Here, we report that G-quadruplex DNA (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 involv...

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Bibliographic Details
Published in:The Journal of neuroscience 2024-04, Vol.44 (15), p.e0093232024
Main Authors: Marshall, Paul R, Davies, Joshua, Zhao, Qiongyi, Liau, Wei-Siang, Lee, Yujin, Basic, Dean, Periyakaruppiah, Ambika, Zajaczkowski, Esmi L, Leighton, Laura J, Madugalle, Sachithrani U, Musgrove, Mason, Kielar, Marcin, Brueckner, Arie Maeve, Gong, Hao, Ren, Haobin, Walsh, Alexander, Kaczmarczyk, Lech, Jackson, Walker S, Chen, Alon, Spitale, Robert C, Bredy, Timothy W
Format: Article
Language:English
Subjects:
Control equipment
Deoxyribonucleic acid
DNA
DNA helicase
DNA structure
Fear conditioning
Molecular modelling
Molecular structure
Transcription activation
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Summary:The conformational state of DNA fine-tunes the transcriptional rate and abundance of RNA. Here, we report that G-quadruplex DNA (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 male C57/BL6 mice. 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. G4-DNA is a molecular switch that enables the temporal regulation of the gene expression underlying the formation of fear extinction memory.
ISSN:0270-6474
1529-2401
1529-2401
DOI:10.1523/JNEUROSCI.0093-23.2024