Cited by 123Genomics and Chromatin DynamicsStress Responses and CortisolHistone Deacetylase Inhibitors Research

Stress-induced epigenetic transcriptional memory of acetylcholinesterase by HDAC4

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Sailaja, Badi Sri, Cohen-Carmon, Dorit, Zimmerman, Gabriel, Soreq, Hermona, Meshorer, Eran·2012·Proceedings of the National Academy of Sciences

Abstract

Stress induces long-lasting changes in neuronal gene expression and cholinergic neurotransmission, but the underlying mechanism(s) are incompletely understood. Here, we report that chromatin structure and histone modifications are causally involved in this transcriptional memory. Specifically, the AChE gene encoding the acetylcholine-hydrolyzing enzyme acetylcholinesterase is known to undergo long-lasting transcriptional and alternative splicing changes after stress. In mice subjected to stress, we identified two alternative 5′ exons that were down-regulated after stress in the hippocampus, accompanied by reduced acetylation and elevated trimethylation of H3K9 at the corresponding promoter. These effects were reversed completely by daily administration of the histone deacetylase (HDAC) inhibitor sodium butyrate for 1 wk after stress. H3K9 hypoacetylation was associated with a selective, sodium butyrate-reversible promoter accumulation of HDAC4. Hippocampal suppression of HDAC4 in vivo completely abolished the long-lasting AChE-related and behavioral stress effects. Our findings demonstrate long-lasting stress-inducible changes in AChE's promoter choices, identify the chromatin changes that support this long-term transcriptional memory, and reveal HDAC4 as a mediator of these effects in the hippocampus.

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Authors
Sailaja, B. S., Cohen-Carmon, D., Zimmerman, G., Soreq, H., & Meshorer, E.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • Departments of aGenetics and
Venue
Proceedings of the National Academy of Sciences
Published
2012-12-10
Volume
109
Issue
52
Pages
E3687-95
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2102812580
Cited by
121
References
47
Citations by year
2026: 2 · 2025: 2 · 2024: 10 · 2023: 7 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 10 · 2018: 5 · 2017: 10 · 2016: 14 · 2015: 14 · 2014: 15 · 2013: 10
FWCI
5.02
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Israel Science Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Keywords
acetylcholinesterase, HDAC4, histone deacetylase, stress, transcriptional memory, alternative splicing, H3K9 acetylation, H3K9 trimethylation, histone modifications, chromatin structure, sodium butyrate, hippocampus, cholinergic neurotransmission, long-term stress effects
MeSH terms
Acetylcholinesterase, Animals, Chromatin, Exons, Hippocampus, Histone Deacetylases, Male, Neurons, Promoter Regions, Genetic, Stress, Physiological, Swimming, Transcription, Genetic, DNA Methylation, Gene Silencing, Epigenesis, Genetic, Mice, Histone Deacetylase Inhibitors

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