Histone Lysine Crotonylation Regulates Long-Term Memory Storage

Utsav Mukherjee; Budhaditya Basu; Stacy E. Beyer; Saaman Ghodsi; Nathan Robillard; Yann Vanrobaeys; Eric B. Taylor; Ted Abel; Snehajyoti Chatterjee

doi:10.1101/2025.02.19.639114

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Histone Lysine Crotonylation Regulates Long-Term Memory Storage

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Histone Lysine Crotonylation Regulates Long-Term Memory Storage

Utsav Mukherjee, Budhaditya Basu, Stacy E. Beyer, Saaman Ghodsi, Nathan Robillard, Yann Vanrobaeys, Eric B. Taylor, Ted Abel and Snehajyoti Chatterjee

bioRxiv

Cold Spring Harbor Laboratory, 1.1

02/19/2025

DOI: 10.1101/2025.02.19.639114

PMCID: PMC11870504

PMID: 40027819

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https://doi.org/10.1101/2025.02.19.639114View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Histone post-translational modifications (PTMs), particularly lysine acetylation (Kac), are critical epigenetic regulators of gene transcription underlying long-term memory consolidation. Beyond Kac, several other non-acetyl acylations have been identified, but their role in memory consolidation remains unknown. Here, we demonstrate histone lysine crotonylation (Kcr) as a key molecular switch of hippocampal memory storage. Spatial memory training induces distinct spatiotemporal patterns of Kcr induction in the dorsal hippocampus of mice. Through genetic and pharmacological manipulations, we show that reducing hippocampal Kcr levels impairs long-term memory, while increasing Kcr enhances memory. Utilizing single-nuclei multiomics, we delineate that Kcr enhancement during memory consolidation activates transcription of genes involved in neurotransmission and synaptic function within hippocampal excitatory neurons. Cell-cell communication analysis further inferred that Kcr enhancement strengthens glutamatergic signaling within principal hippocampal neurons. Our findings establish Kcr as a novel epigenetic mechanism governing memory consolidation and provide a foundation for therapeutic strategies targeting memory-related disorders.

Neuroscience

Details

Title: Subtitle: Histone Lysine Crotonylation Regulates Long-Term Memory Storage
Creators: Utsav Mukherjee - University of Iowa
Budhaditya Basu - University of Iowa
Stacy E. Beyer - University of Iowa
Saaman Ghodsi - University of Iowa
Nathan Robillard - University of Iowa
Yann Vanrobaeys - University of Iowa
Eric B. Taylor - University of Iowa
Ted Abel - University of Iowa
Snehajyoti Chatterjee - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
Edition: 1.1
DOI: 10.1101/2025.02.19.639114
PMID: 40027819
PMCID: PMC11870504
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Number of pages: 35
Language: English
Date posted: 02/19/2025
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984798229102771

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