DNA G-Quadruplex Is a Transcriptional Control Device That Regulates Memory
- Paul R. Marshall1,2,
- Joshua Davies1,
- Qiongyi Zhao1,
- Wei-Siang Liau1,
- Yujin Lee1,
- Dean Basic1,
- Ambika Periyakaruppiah1,
- Esmi L. Zajaczkowski1,
- Laura J. Leighton1,
- Sachithrani U. Madugalle1,
- Mason Musgrove1,
- Marcin Kielar1,
- Arie Maeve Brueckner1,
- Hao Gong1,
- Haobin Ren1,
- Alexander Walsh1,
- Lech Kaczmarczyk3,
- Walker S. Jackson3,
- Alon Chen4,
- Robert C. Spitale5, and
- Timothy W. Bredy1
- 1Cognitive Neuroepigenetics Laboratory, The Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
- 2Genome Sciences and Cancer Division & Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra 2601, Australia
- 3Department of Biomedical and Clinical Sciences (BKV), Division of Neurobiology (NEURO), Linköping University, Linköping 581 83, Sweden
- 4Neurobiology of Stress Laboratory, Department Brain Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
- 5Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California 92697
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Author contributions: P.R.M., E.L.Z., and T.W.B. designed research; P.R.M., J.D., Q.Z., W.-S.L., Y.L., D.B., A.P., E.L.Z., L.J.L., S.U.M., M.M., M.K., A.M.B., H.G., H.R., and A.W. performed research; P.R.M., J.D., Q.Z., W.-S.L., D.B., and A.W. analyzed data; W.-S.L., M.K., L.K., W.S.J., A.C., and R.C.S. contributed unpublished reagents/analytic tools; T.W.B. wrote the paper.
Abstract
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.
- Received January 17, 2023.
- Revision received February 14, 2024.
- Accepted February 20, 2024.
- Copyright © 2024 the authors
