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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.

Original publication

DOI

10.1038/s41467-017-02748-x

Type

Journal article

Journal

Nat Commun

Publication Date

19/01/2018

Volume

9

Keywords

Animals, Animals, Newborn, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Conditioning, Psychological, DNA, DNA Methylation, Dentate Gyrus, 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