To our knowledge, these epigenetic and transcriptional profiles constitute the first tiling microarray data set exploring the relationship between epigenetic modifications and RNA expression in both protein coding and non-coding regions across a chromosomal locus in the mammalian brain. High vs Low LG adult offspring) and performed an analysis of DNA methylation, H3K9 acetylation and gene expression of a contiguous 7 million base pair region of rat chromosome 18 containing the NR3C1 gene at 100 bp spacing. We obtained hippocampal samples from the adult offspring of rat mothers that differed in the frequency of pup licking/grooming in the first week of life (i.e. In the present study, we test this hypothesis by examining epigenetic and transcriptional changes associated with naturally occurring differences in maternal care. The fact that a large number of genes are responsive to the effects of TSA and L-methionine implies that the epigenetic regulation of gene expression as a function of maternal care may be extensive. The fact that the methyl donor L-methionine inhibits some of the genes influenced by maternal behavior supports the involvement of either DNA or histone methylation. Some of these changes in gene expression can be reversed by pharmacological alterations of chromatin structure by the histone deacetylase inhibitor Trichostatin A (TSA) and the methyl donor L-methionine. There is evidence that the expression of hundreds of additional genes in adult rats changes in response to differences in maternal care. In rats, variations in maternal care in the first week of life are associated with alterations in DNA methylation and H3K9 acetylation of the NR3C1 promoter region, and gene expression of the GR1 7 splice variant of the NR3C1 gene in the hippocampus of adult offspring. In rats and humans, there is evidence that changes in gene expression as a function of early care are at least partly regulated by epigenetic mechanisms. These effects are reversed by cross-fostering,, demonstrating a causal link between maternal care and gene expression programming. Naturally occurring variations in maternal care in the first week of life in rats are associated with changes in brain and behavior that persist until adulthood. Studies in the rat directly link the maternal care environment to long-term effects on neural systems that regulate stress, emotional function, , learning and memory, , and neuroplasticity,. The quality of parental care has a broad impact on mental health, including the risk for psychopathology, ,.
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