DNA G-Quadruplex Is a Transcriptional Control Device That Regulates Memory
Paul R. Marshall, Joshua Davies, Qiongyi Zhao, Wei‐Siang Liau, Yujin Lee, Dean Basic, Ambika Periyakaruppiah, Esmi L. Zajaczkowski, Laura J. Leighton, Sachithrani U. Madugalle, Mason Musgrove, Marcin Kielar, Arie Maeve Brueckner, Hao Gong, Haobin Ren, Alexander C. Walsh, Lech Kaczmarczyk, Walker S. Jackson, Alon Chen, Robert C. Spitale, Timothy W. Bredy
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.