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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
The Journal of neuroscience, 04/2024, Letnik: 44, Številka: 15Journal Article
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.
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