期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 14, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2021.664912
关键词
environmental enrichment; epigenetics; 3D genome organization; learning; postnatal development; chromatin accessibility; Hi-C; inter-chromosomal contacts
资金
- Spanish Ministry of Economy and Competitiveness [SAF2011-26216]
- Centro de Excelencia Severo Ochoa 2017-2021 [SEV-20160571]
- CERCA Programme/Generalitat de Catalunya
- Swiss National Science Foundation Fellowship [PBLAP3_136878]
- Marie Curie Actions
- U.S. National Institutes of Mental Health Funds [R01MH104341, R01MH117790]
- Social Sciences and Humanities Research Council of Canada [NFRFE-201801305]
- Spanish Ministry of Science and Innovation
- Agencia Estatal de Investigacion [PID2019-110755RBI00/AEI/10.13039/501100011033]
- European Union's Horizon 2020 Research and Innovation programme [848077]
- Jerome Lejeune Foundation
- NIH [1R01EB 02815901]
- Marato TV3 [2016/20-30]
- University of Tubingen
- [R01GM109215]
- Swiss National Science Foundation (SNF) [PBLAP3_136878] Funding Source: Swiss National Science Foundation (SNF)
The study used environmental enrichment (EE) paradigm in young mice to investigate how environmental stimulation impacts epigenome and genome organization. The findings suggest that environmental stimuli can lead to changes in chromatin accessibility, gene regulation, and 3D genome conformation, affecting transcriptional programs required for neuronal development.
In early development, the environment triggers mnemonic epigenomic programs resulting in memory and learning experiences to confer cognitive phenotypes into adulthood. To uncover how environmental stimulation impacts the epigenome and genome organization, we used the paradigm of environmental enrichment (EE) in young mice constantly receiving novel stimulation. We profiled epigenome and chromatin architecture in whole cortex and sorted neurons by deep-sequencing techniques. Specifically, we studied chromatin accessibility, gene and protein regulation, and 3D genome conformation, combined with predicted enhancer and chromatin interactions. We identified increased chromatin accessibility, transcription factor binding including CTCF-mediated insulation, differential occupancy of H3K36me3 and H3K79me2, and changes in transcriptional programs required for neuronal development. EE stimuli led to local genome re-organization by inducing increased contacts between chromosomes 7 and 17 (inter-chromosomal). Our findings support the notion that EE-induced learning and memory processes are directly associated with the epigenome and genome organization.
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