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

J Neurosci. 2024 Apr 10;44(15):e0093232024. doi: 10.1523/JNEUROSCI.0093-23.2024.

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.

Keywords: DNA; gene expression; memory.

MeSH terms

  • Animals
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DNA / metabolism
  • Extinction, Psychological
  • Fear
  • G-Quadruplexes*
  • Male
  • Mice

Substances

  • DEAD-box RNA Helicases
  • DNA