Environmental Enrichment Induces Epigenomic and Genome Organization Changes Relevant for Cognition

Sergio Espeso-Gil; Aliaksei Z Holik; Sarah Bonnin; Shalu Jhanwar; Sandhya Chandrasekaran; Roger Pique-Regi; Júlia Albaigès-Ràfols; Michael Maher; Jon Permanyer; Manuel Irimia; Marc R Friedländer; Meritxell Pons-Espinal; Schahram Akbarian; Mara Dierssen; Philipp G Maass; Charlotte N Hor; Stephan Ossowski

doi:10.3389/fnmol.2021.664912

Environmental Enrichment Induces Epigenomic and Genome Organization Changes Relevant for Cognition

Front Mol Neurosci. 2021 May 5:14:664912. doi: 10.3389/fnmol.2021.664912. eCollection 2021.

Authors

Sergio Espeso-Gil^{1

2

3}, Aliaksei Z Holik¹, Sarah Bonnin¹, Shalu Jhanwar^{1

2}, Sandhya Chandrasekaran^{4

5}, Roger Pique-Regi⁶, Júlia Albaigès-Ràfols^{1

2}, Michael Maher^{1

2

2}, Jon Permanyer¹, Manuel Irimia^{1

2

7}, Marc R Friedländer⁸, Meritxell Pons-Espinal^{1

2}, Schahram Akbarian⁵, Mara Dierssen^{1

2}, Philipp G Maass^{3

9}, Charlotte N Hor^{1

2}, Stephan Ossowski^{1

2}

Affiliations

¹ Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
² Universitat Pompeu Fabra (UPF), Barcelona, Spain.
³ Genetics and Genome Biology Program, SickKids Research Institute, Toronto, ON, Canada.
⁴ MD/PhD Program in the Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁵ Department of Psychiatry and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁶ Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States.
⁷ ICREA, Pg. Lluis Companys 23, Barcelona, Spain.
⁸ Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
⁹ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

Abstract

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.

Keywords: 3D genome organization; Hi-C; chromatin accessibility; environmental enrichment; epigenetics; inter-chromosomal contacts; learning; postnatal development.

Abstract

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