title: 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. We compare these profiles to corresponding DNA methylation profiles in rats that received differential levels of maternal care. The profiles of both species reveal hundreds of DNA methylation differences associated with early life experience distributed across the entire region in nonrandom patterns. For instance, methylation differences tend to cluster by genomic location, forming clusters covering as many as 1 million bases. Even more surprisingly, these differences seem to specifically target regulatory regions such as gene promoters, particularly those of the protocadherin α, β, and γ gene families. Beyond these high-level similarities, more detailed analyses reveal methylation differences likely stemming from the significant biological and environmental differences between species. These results provide support for an analogous cross-species epigenetic regulatory response at the level of the genomic region to early life experience.
authors.affiliation: Sackler Program for Epigenetics and Developmental Psychobiology at McGill University, Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Suderman
authors.forename: Patrick O
authors.initials: PO
authors.lastname: McGowan
authors.forename: Aya
authors.initials: A
authors.lastname: Sasaki
authors.forename: Tony C T
authors.initials: TC
authors.lastname: Huang
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hallett
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D002648:Child; D002649:Child Abuse / Q000523:psychology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D059647:Gene-Environment Interaction; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008016:Life Change Events; D008297:Male; D005810:Multigene Family; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics; D013045:Species Specificity
chemical_list: D015820:Cadherins; C497713:NR3C1 protein, human; C542344:NR3C1 protein, rat; D011965:Receptors, Glucocorticoid