TY - JOUR
T1 - DNA G-Quadruplex Is a Transcriptional Control Device That Regulates Memory
AU - Marshall, Paul R.
AU - Davies, Joshua
AU - Zhao, Qiongyi
AU - Liau, Wei Siang
AU - Lee, Yujin
AU - Basic, Dean
AU - Periyakaruppiah, Ambika
AU - Zajaczkowski, Esmi L.
AU - Leighton, Laura J.
AU - Madugalle, Sachithrani U.
AU - Musgrove, Mason
AU - Kielar, Marcin
AU - Brueckner, Arie Maeve
AU - Gong, Hao
AU - Ren, Haobin
AU - Walsh, Alexander
AU - Kaczmarczyk, Lech
AU - Jackson, Walker S.
AU - Chen, Alon
AU - Spitale, Robert C.
AU - Bredy, Timothy W.
N1 - We thank Ms. Rowan Tweedale for the helpful editing of the manuscript. Australian Research Council GA142202 (T.W.B.).
Publisher Copyright:
© 2024 Society for Neuroscience. All rights reserved.
PY - 2024/4/10
Y1 - 2024/4/10
N2 - 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. One-Sentence Summary: G4-DNA is a molecular switch that enables the temporal regulation of the gene expression underlying the formation of fear extinction memory.
AB - 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. One-Sentence Summary: G4-DNA is a molecular switch that enables the temporal regulation of the gene expression underlying the formation of fear extinction memory.
UR - http://www.scopus.com/inward/record.url?scp=85190088001&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0093-23.2024
DO - 10.1523/JNEUROSCI.0093-23.2024
M3 - Article
C2 - 38418220
AN - SCOPUS:85190088001
SN - 0270-6474
VL - 44
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 15
M1 - e0093232024
ER -