エピジェネティクスで記憶のON/OFF切り替えに成功(Switching memories on and off with epigenetics)

2025-10-30 スイス連邦工科大学ローザンヌ校(EPFL)

<関連情報>

• https://actu.epfl.ch/news/switching-memories-on-and-off-with-epigenetics/
• https://www.nature.com/articles/s41588-025-02368-y

記憶発現における細胞型および遺伝子座特異的なエピジェネティック編集 Cell-type- and locus-specific epigenetic editing of memory expression

Davide M. Coda,Lisa Watt,Liliane Glauser,Mykhailo Y. Batiuk,Allison M. Burns,Cora L. Stahl,Lok Y. Wong & Johannes Gräff
Nature Genetics  Published:29 October 2025
DOI:https://doi.org/10.1038/s41588-025-02368-y

Abstract

Epigenetic mechanisms have long been proposed to act as molecular mnemonics^1,2,3, but whether the epigenetic makeup of a single genomic site can guide learnt behaviors remains unknown. Here we combined CRISPR-based epigenetic editing tools^4,5 with c-Fos-driven engram technologies^6,7 to address this question in memory-bearing neuronal ensembles. Focusing on the promoter of Arc, which encodes a master regulator of synaptic plasticity⁸, we found that its locus-specific and temporally controlled epigenetic editing is necessary and sufficient to regulate memory expression. Such effects occurred irrespective of the memory phase—during the initially labile period after learning and for fully consolidated memories—and were reversible within subject, testifying to their inherent plasticity. These findings provide a proof-of-principle that site-specific epigenetic dynamics are causally implicated in memory expression.