Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus.
Title | Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Zhang 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 |
Journal | Nat Commun |
Volume | 9 |
Issue | 1 |
Pagination | 298 |
Date Published | 2018 01 19 |
ISSN | 2041-1723 |
Keywords | Animals, 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. |
DOI | 10.1038/s41467-017-02748-x |
Alternate Journal | Nat Commun |
PubMed ID | 29352183 |
PubMed Central ID | PMC5775256 |
Grant List | R00 NS080911 / NS / NINDS NIH HHS / United States T32 MH020002 / MH / NIMH NIH HHS / United States |