Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble
Name
nihms-1625718.pdf
Description
Accepted version
Size
5.18 MB
Format
Adobe PDF
Checksum (MD5)
b8750ef4871442eda3b4b4769d5f9a87
Author(s)
Marco, Asaf
Meharena, Hiruy S.
Dileep, Vishnu
Raju, Ravikiran M.
Davila Velderrain, Jose
Zhang, Amy Letao
Adaikkan, Chinnakkaruppan
Young, Jennie Zin-Ney
Gao, Fan
Kellis, Manolis
Date Issued
October 2020
Journal
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Citation
Marco, Asaf et al. "Mapping the epigenomic and transcriptomic interplay during memory formation and recall in the hippocampal engram ensemble." Nature Neuroscience 23, 12 (October 2020): 1606–1617. © 2020 The Author(s)
Version
Author's final manuscript
Abstract
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.
MIT Department
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41593-020-00717-0
