Cognitive Neuroepigenetics Laboratory, The Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia
Genome Sciences and Cancer Division & Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra 2601, Australia.
J Neurosci. 2024 Apr 10;44(15):e0093232024. doi: 10.1523/JNEUROSCI.0093-23.2024.
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.
DNA 的构象状态精细调节 RNA 的转录速率和丰度。在这里,我们报告说,G-四链体 DNA(G4-DNA)以经验依赖的方式在神经元中积累,并且这对于在雄性 C57/BL6 小鼠中参与学习和记忆的基因的瞬时沉默和激活是必需的。此外,通过 dCas9 介导的解旋酶 DHX36 的沉积来特异性解决 G4-DNA 会损害恐惧消退记忆。因此,动态 DNA 结构状态代表了记忆巩固的关键分子机制。G4-DNA 是一种分子开关,可实现恐惧消退记忆形成所涉及的基因表达的时间调节。