Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus

Tie-Yuan Zhang (), Christopher L. Keown, Xianglan Wen, Junhao Li, Dulcie A. Vousden, Christoph Anacker, Urvashi Bhattacharyya, Richard Ryan, Josie Diorio, Nicholas O’Toole, Jason P. Lerch, Eran A. Mukamel () and Michael J. Meaney
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Tie-Yuan Zhang: McGill University
Christopher L. Keown: University of California
Xianglan Wen: McGill University
Junhao Li: University of California
Dulcie A. Vousden: University of Toronto
Christoph Anacker: McGill University
Urvashi Bhattacharyya: University of California
Richard Ryan: McGill University
Josie Diorio: McGill University
Nicholas O’Toole: McGill University
Jason P. Lerch: University of Toronto
Eran A. Mukamel: University of California
Michael J. Meaney: McGill University

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Early life experience influences stress reactivity and mental health through effects on cognitive-emotional functions that are, in part, linked to gene expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus (DG) is a major site for experience-dependent plasticity associated with sustained transcriptional alterations, potentially mediated by epigenetic modifications. Here, we report comprehensive DNA methylome, hydroxymethylome and transcriptome data sets from mouse dorsal and ventral DG. We find genome-wide transcriptional and methylation differences between dorsal and ventral DG, including at key developmental transcriptional factors. Peripubertal environmental enrichment increases hippocampal volume and enhances dorsal DG-specific differences in gene expression. Enrichment also enhances dorsal-ventral differences in DNA methylation, including at binding sites of the transcription factor NeuroD1, a regulator of adult neurogenesis. These results indicate a dorsal-ventral asymmetry in transcription and methylation that parallels well-known functional and anatomical differences, and that may be enhanced by environmental enrichment.

Date: 2018
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DOI: 10.1038/s41467-017-02748-x

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