DNA G-quadruplex is a transcriptional control device that regulates memory

Marshall, P. R.; Zhao, Q.; Davies, J.; Liau, W.-S.; Lee, Y.; Basic, D.; Periyakaruppiah, A.; Zajaczkowski, E.; Leighton, L. J.; Madugalle, S. U.; Musgrove, M.; Kielar, M.; Gong, H.; Ren, H.; Kaczmarczyk, L.; Jackson, W. S.; Chen, A.; Spitale, R.; Bredy, T.

doi:10.1101/2023.01.09.523337

bioRxiv · 10.1101/2023.01.09.523337

DNA G-quadruplex is a transcriptional control device that regulates memory

Marshall, P. R.·Zhao, Q.·Davies, J.·Liau, W.-S.·Lee, Y.·Basic, D.·Periyakaruppiah, A.·Zajaczkowski, E.·Leighton, L. J.·Madugalle, S. U.·Musgrove, M.·Kielar, M.·Gong, H.·Ren, H.·Kaczmarczyk, L.·Jackson, W. S.·Chen, A.·Spitale, R.·Bredy, T.

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Abstract

The conformational state of DNA fine-tunes the transcriptional rate and abundance of RNA. Here we report that DNA G-quadruplex (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 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 SummaryG4-DNA is a molecular switch that enables the temporal regulation of the gene expression underlying the formation of fear extinction memory.

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Marshall, P. R., Zhao, Q., Davies, J., Liau, W.-S., Lee, Y., Basic, D., Periyakaruppiah, A., Zajaczkowski, E., Leighton, L. J., Madugalle, S. U., Musgrove, M., Kielar, M., Gong, H., Ren, H., Kaczmarczyk, L., Jackson, W. S., Chen, A., Spitale, R., Bredy, T.. 2023-01-10. DNA G-quadruplex is a transcriptional control device that regulates memory. https://doi.org/10.1101/2023.01.09.523337

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