Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus

ABSTRACT: Early life experience is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (glucocorticoid receptor) gene in the hippocampus of both rats and humans. However, it is unlikely that such effects completely capture the evolutionarily conserved epigenetic mechanisms of early adaptation to environment. Here we present DNA methylation profiles spanning 6.5 million base pairs centered at the NR3C1 gene in the hippocampus of humans who experienced abuse as children and nonabused controls. Hippocampal samples were obtained from the Quebec Suicide Brain Bank and included 10 suicide subjects with histories of severe childhood abuse and 9 controls with validated negative histories of childhood abuse who did not differ in postmortem interval, sex, age at death, or brain pH (all P > 0.05). Using custom-designed microarrays with probes tiling the 6.5 million base pair region of human chromosome 5 centered at the NR3C1 gene at 100 bp spacing, we obtained DNA methylation profiles by MeDIP-chip. Replicates were performed.

ORGANISM(S): Homo sapiens

SUBMITTER: Matthew Suderman

PROVIDER: E-GEOD-38352 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Animal and human studies suggest that inflammation is associated with behavioral disorders including aggression. We have recently shown that physical aggression of boys during childhood is strongly associated with reduced plasma levels of cytokines IL-1a, IL-4, IL-6, IL-8 and IL-10, later in early adulthood (Provencal et al., unpublished data). This study tests the hypothesis that there is an association between differential DNA methylation regions in cytokine genes in T cells and monocytes DNA in adult subjects and a trajectory of physical aggression from childhood to adolescence. We compared the methylation profiles of the entire genomic loci encompassing the IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6 genes in adult males on a chronic physical aggression trajectory (CPA) and males with the same background who followed a normal physical aggression trajectory (control group). We used the method of methylated DNA immunoprecipitation (MeDIP) with comprehensive cytokine gene loci and TF loci microarray hybridization, statistical analysis and false discovery rate correction. We recruited two groups of Caucasian males who were born in families with a low socioeconomic status and were living at the time of the present study within 200km from our laboratory. The first group, composed of 8 subjects, had a history of chronic physical aggression from age 6 to 15 years (chronic physical aggression group, CPA). The second group, composed of 12 subjects, was recruited from the same longitudinal studies but included only those who did not have a history of chronic physical aggression from age 6 to 15 (Control group, CG). Using custom-designed microarrays with 44K probes tiling cytokines IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6, we obtained DNA methylation profiles by meDIP-chip. Each profile was generated in triplicate.

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Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus

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