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Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble
Open accessAbstract
The epigenome and three-dimensional (3D) genomic architecture are emerging as key factors in the dynamic regulation of different transcriptional programs required for neuronal functions. In this study, we used an activity-dependent tagging system in mice to determine the epigenetic state, 3D genome architecture and transcriptional landscape of engram cells over the lifespan of memory formation and recall. Our findings reveal that memory encoding leads to an epigenetic priming event, marked by increased accessibility of enhancers without the corresponding transcriptional changes. Memory consolidation subsequently results in spatial reorganization of large chromatin segments and promoter-enhancer interactions. Finally, with reactivation, engram neurons use a subset of de novo long-range interactions, where primed enhancers are brought in contact with their respective promoters to upregulate genes involved in local protein translation in synaptic compartments. Collectively, our work elucidates the comprehensive transcriptional and epigenomic landscape across the lifespan of memory formation and recall in the hippocampal engram ensemble.
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“There is now emerging evidence that the 3D genome is actively regulated during learning and memory formation”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [39]
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“The 3D genome plays an important role in neuronal gene expression and function”
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Metadata
- Authors
- Marco, A., Meharena, H. S., Dileep, V., Raju, R. M., Davila-Velderrain, J., Zhang, A. L., Adaikkan, C., Young, J. Z., Gao, F., Kellis, M., & Tsai, L.-H.
- Affiliations
- Massachusetts Institute of Technology (US)
- Boston Children's Hospital (US)
- Broad Institute (US)
- Corresponding author
- Marco, Asaf
- Tsai, Li-Huei
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2020-10-05
- Volume
- 23
- Issue
- 12
- Pages
- 1606-1617
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC7686266
- OpenAlex
- W3090072122
- Cited by
- 159
- References
- 68
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 30 · 2023: 22 · 2022: 32 · 2021: 19 · 2020: 2
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Alzheimer's Association (AARF-19-618751)
- JPB Foundation
- Cure Alzheimer's Fund
- Down Syndrome Research Foundation
- National Institutes of Health (NIH T32, T32 grant)
- National Institute on Aging (R01AG058002, R01AG062335, RF1AG054012, RF1AG062377, R01AG067151)
- National Institute of Mental Health (U01MH119509, R01MH109978)
- National Human Genome Research Institute (R01HG008155, U24HG009446)
- National Institute of Neurological Disorders and Stroke (U01NS110453, R01NS102730, UG3NS115064)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD098061)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- memory formation, memory retrieval, epigenome, 3D genome organization, enhancer accessibility, enhancer-promoter interactions, long-range chromatin interactions, memory consolidation, memory reactivation, transcriptional regulation, mRNA translation
- MeSH terms
- Memory Consolidation, Animals, Brain Mapping, Hippocampus, Memory, Mice, Transgenic, Neurons, Mental Recall, Synapses, Up-Regulation, Mice, Epigenomics, Transcriptome
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