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

TitleEnvironmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus.
Publication TypeJournal Article
Year of Publication2018
AuthorsZhang T-Y, Keown CL, Wen X, Li J, Vousden DA, Anacker C, Bhattacharyya U, Ryan R, Diorio J, O'Toole N, Lerch JP, Mukamel EA, Meaney MJ
JournalNat Commun
Volume9
Issue1
Pagination298
Date Published2018 01 19
ISSN2041-1723
KeywordsAnimals, Animals, Newborn, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Conditioning (Psychology), Dentate Gyrus, DNA, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Gene-Environment Interaction, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins, Neurogenesis, Neuronal Plasticity, Neurons, Protein Binding, Transcriptome
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.

DOI10.1038/s41467-017-02748-x
Alternate JournalNat Commun
PubMed ID29352183
PubMed Central IDPMC5775256
Grant ListR00 NS080911 / NS / NINDS NIH HHS / United States
T32 MH020002 / MH / NIMH NIH HHS / United States

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