Genome-wide 5mC and 5hmC DNA profile of the hippocampus of maternally deprived rats

Early life experiences cause life-long changes in gene expression which may affect health later on in life. Maternal deprivation (MD) in rodents mimics traumatic early life experiences, and induces lifelong behavioural, immunological, and gene expression changes. Expanding on our previous report of increased hippocampal Nr3c1 mRNA levels after MD, here we present complete 5-methyl Cytosine (5mC) and 5-hydroxymethyl Cytosine (5hmC) epigenomes from the hippocampus of MD rats as well as handling (HD) or undisturbed control (C) animals. The 5mC and 5hmC profiles were highly concordant between treatment groups, however 50 differentially methylated regions (DMR) and 71 DhMR were identified. Both DMR and D(h)MR were principally intergenic, >200kbp from annotated gene loci, including for many stress-related genes (Bdnf, Avp, Crh, Nr3cl, Nr4a1 and Igf2). The differentially methylated regions were, however, in close proximity to piRNA loci. Together with Piwi proteins, piRNAs form complexes that are mainly known for their role in transposon and gene expression regulation, particularly on the epigenetic level. Our data shows that MD and HD induced clear differential methylation that was associated primarily with regulatory RNA rather than gene loci. We suggest that the phenotypic differences in our maternal handling model were most probably due to post-transcriptional processes rather than direct regulation of specific target genes.