title: Environmental enrichment modulates 5-hydroxymethylcytosine dynamics in hippocampus.
abstract: Gene-environment interactions mediated at the epigenetic level may provide an initial step in delivering an appropriate response to environmental changes. 5-Hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC), accounts for ~40% of modified cytosine in the brain and has been implicated in DNA methylation-related plasticity. To identify the role of 5hmC in gene-environment interactions, we exposed both young (6-week-old) and aged (18-month-old) mice to both an enriched environment and a standard environment. Exposure to EE significantly improves learning and memory in aged mice and reduces 5hmC abundance in mouse hippocampus. Furthermore, we mapped the genome-wide distribution of 5hmC and found that the alteration of 5hmC modification occurred mainly at gene bodies. In particular, genes involved in axon guidance are enriched among the genes with altered 5hmC modification. These results together suggest that environmental enrichment could modulate the dynamics of 5hmC in hippocampus, which could potentially contribute to improved learning and memory in aged animals.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Hasan
authors.initials: H
authors.lastname: Irier
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: R Craig
authors.initials: RC
authors.lastname: Street
authors.affiliation: Williams College, Williamstown, MA 01267, USA.
authors.forename: Ronak
authors.initials: R
authors.lastname: Dave
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Timothy Hayden
authors.initials: TH
authors.lastname: Davis
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: peng.jin@emory.edu.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism* / Q000031:analogs & derivatives; D000375:Aging; D000818:Animals; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D005786:Gene Expression Regulation; D059647:Gene-Environment Interaction; D006624:Hippocampus / Q000378:metabolism*; D007858:Learning; D051379:Mice
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 5hmC; Axon guidance; DNA methylation; Enriched environment; Epigenetics