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Publication : Cell-type- and locus-specific epigenetic editing of memory expression.

First Author  Coda DM Year  2025
Journal  Nat Genet Volume  57
Issue  11 Pages  2661-2668
PubMed ID  41162785 Mgi Jnum  J:375479
Mgi Id  MGI:8264905 Doi  10.1038/s41588-025-02368-y
Citation  Coda DM, et al. (2025) Cell-type- and locus-specific epigenetic editing of memory expression. Nat Genet 57(11):2661-2668
abstractText  Epigenetic mechanisms have long been proposed to act as molecular mnemonics(1-3), 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 plasticity(8), 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.
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