Learning and Age-Related Changes in Genome-wide H2A.Z Binding in the Mouse Hippocampus
Open accessAbstract
Histone variants were recently discovered to regulate neural plasticity, with H2A.Z emerging as a memory suppressor. Using whole-genome sequencing of the mouse hippocampus, we show that basal H2A.Z occupancy is positively associated with steady-state transcription, whereas learning-induced H2A.Z removal is associated with learning-induced gene expression. AAV-mediated H2A.Z depletion enhanced fear memory and resulted in gene-specific alterations of learning-induced transcription, reinforcing the role of H2A.Z as a memory suppressor. H2A.Z accumulated with age, although it remained sensitive to learning-induced eviction. Learning-related H2A.Z removal occurred at largely distinct genes in young versus aged mice, suggesting that H2A.Z is subject to regulatory shifts in the aged brain despite similar memory performance. When combined with prior evidence of H3.3 accumulation in neurons, our data suggest that nucleosome composition in the brain is reorganized with age.
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Previous studies have shown the importance of histones in DNA damage response, senescence, brain aging, neuronal identity, and memory formation.
“Previous studies have shown the importance of histones in DNA damage response, senescence, brain aging, neuronal identity, and memory formation100–102,136–139.”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [101]
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Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice
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Critical Role of Histone Turnover in Neuronal Transcription and Plasticity
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Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice
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DNA methylation aging clocks: challenges and recommendations
Bell, C. G., Lowe, R., Adams, P. D., Baccarelli, A. A., Beck, S., Bell, J. T., Christensen, B. C., Gladyshev, V. N., Heijmans, B. T., Horvath, S., et al. (2019) · Genome Biology · doi:10.1186/s13059-019-1824-y · Cited by 1,025 · see citing works
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- Authors
- Stefanelli, G., Azam, A. B., Walters, B. J., Brimble, M. A., Gettens, C. P., Bouchard-Cannon, P., Cheng, H.-Y. M., Davidoff, A. M., Narkaj, K., Day, J. J., Kennedy, A. J., & Zovkic, I. B.
- Affiliations
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- St. Jude Children's Research Hospital (US)
- Bates College (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Kennedy, Andrew J.
- Zovkic, Iva B.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 22
- Issue
- 5
- Pages
- 1124-1131
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5820781
- OpenAlex
- W2786912169
- Cited by
- 98
- References
- 3
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 10 · 2022: 10 · 2021: 12 · 2020: 12 · 2019: 17 · 2018: 7
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R00DA034681, P20GM103423, DP1DA039650)
- Connaught Fund
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- H2A.Z, histone variants, hippocampus, fear memory, memory suppression, age-related changes, histone H3.3, neuroplasticity, chromatin regulation
- MeSH terms
- Aging, Animals, Gene Expression Regulation, Hippocampus, Histones, Learning, Male, Mice, Inbred C57BL, Nucleosomes, Mice
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