Official websites use. Share sensitive information only on official, secure websites. Our genome adapts to environmental influences, in part through epigenetic mechanisms, including DNA methylation. Variations in the quality of the early environment are associated with alterations in DNA methylation in rodents, and recent data suggest similar processes in humans in response to early-life adversity.
Genome-wide study of promoter methylation in individuals with severe abuse during childhood. Promoter DNA methylation levels were profiled using methylated DNA immunoprecipitation followed by microarray hybridization in hippocampal tissue from 41 French-Canadian men 25 with a history of severe childhood abuse and 16 control subjects. Methylation profiles were compared with corresponding genome-wide gene expression profiles obtained by messenger RNA microarrays.
Methylation differences between groups were validated on neuronal and nonneuronal DNA fractions isolated by fluorescence-assisted cell sorting. Functional consequences of site-specific promoter methylation were assessed by luciferase assays. We identified differentially methylated promoters in individuals with a history of abuse compared with controls. Among these promoters, showed hypermethylation and demonstrated hypomethylation.
Validation and site-specific quantification of DNA methylation in the 5 most hypermethylated gene promoters indicated that methylation differences occurred mainly in the neuronal cellular fraction.
Methylated ALS2 constructs mimicking the methylation state in samples from abused suicide completers showed decreased promoter transcriptional activity associated with decreased hippocampal expression of ALS2 variants. Childhood adversity is associated with epigenetic alterations in the promoters of several genes in hippocampal neurons. Childhood adversity, characterized by the presence of sexual and physical abuse, is a global problem of significant proportions. Childhood sexual abuse and childhood physical abuse are among the strongest predictors of psychiatric pathology and severity of clinical course, including suicide.
