Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE38352 | GEO | 2012/05/31
SECONDARY ACCESSION(S): PRJNA167744
REPOSITORIES: GEO
Similar Datasets
Project description: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.
2012-05-30 | E-GEOD-38352 | biostudies-arrayexpress
Project description:Maternal care 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, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care. We obtained hippocampal samples from adult offspring of rat mothers that differed in the frequency of pup licking/grooming in the first week of life. Using custom-designed microarrays with probes tiling the 7 million base pair region of rat chromosome 18 centered at the NR3C1 gene at 100 bp spacing, we obtained DNA methylation and H3K9 acetylation profiles by ChIP-on-chip. Each profile was generated in triplicate, each type of profile from 3 high frequency and 3 low frequency mothers.
2011-03-09 | E-GEOD-20714 | biostudies-arrayexpress
Project description:Maternal care 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, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care. We obtained hippocampal samples from adult offspring of rat mothers that differed in the frequency of pup licking/grooming in the first week of life, 4 from high frequency and 4 from low frequency mothers. Using custom-designed microarrays with probes tiling the 7 million base pair region of rat chromosome 18 centered at the NR3C1 gene at 100 bp spacing, we obtained transcription profiles by hybridizing cDNA to microarrays. Each profile was generated in duplicate.
2011-03-09 | E-GEOD-20717 | biostudies-arrayexpress
Project description:Maternal care 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, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care.
2011-03-09 | GSE20717 | GEO
Project description:Maternal care 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, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care.
2011-03-09 | GSE20714 | GEO
Project description:Environmental factors, including substance abuse and stress, cause long-lasting changes in the regulation of gene expression in the brain via epigenetic mechanisms, such as DNA methylation. We examined genome-wide DNA methylation patterns in the prefrontal cortex (PFC, BA10) of 25 pairs of control and individuals with AUD, using the Infinium® MethylationEPICBeadChip. We identified 5,254 differentially methylated CpGs (pnominal<0.005). Bioinformatic analyses highlighted biological processes containing genes related to stress adaptation, including the glucocorticoid receptor (encoded by NR3C1). Considering that alcohol is a stressor, we focused our attention on differentially methylated regions of the NR3C1 gene and validated the differential methylation of several genes in the NR3C1 network. We observed that chronic alcohol drinking results in a significant increased methylation of the NR3C1 exon variant 1H, with a particular increase in the levels of 5-hydroxymethylcytosine over 5-methylcytosine. These changes in DNA methylation were associated with reduced NR3C1 mRNA and protein levels in PFC as well as other cortico-limbic regions of AUD subjects when compared to controls. Furthermore, we show that the expression of several stress-responsive genes (e.g., CRF, POMC, FKBP5) is altered in the PFC of AUD subjects. These stress-response genes were also changed in the hippocampus, a region that is highly susceptible to stress. These data suggest that alcohol-dependent aberrant DNA methylation of NR3C1 and consequent changes in other stress-related genes might be fundamental in the pathophysiology of AUD and lay the groundwork for treatments targeting the epigenetic mechanisms regulating NR3C1 in AUD.
2019-12-31 | GSE128401 | GEO
Project description:Adverse experiences in childhood are associated with altered hypothalamic pituitary adrenal axis function and negative health outcomes throughout life. It is now commonly accepted that abuse and neglect can alter epigenetic regulation of HPA genes. Accumulated evidence suggests harsh parenting practices such as spanking are also strong predictors of negative health outcomes. We predicted harsh parenting at 2.5 years old would predict HPA gene DNA methylation similarly to abuse and neglect, and cortisol output at 8.5 years old. Saliva samples were collected three times a day across three days to estimate cortisol diurnal slopes. Methylation was quantified using the Illumina Infinium MethylationEPIC array BeadChip (850K) with DNA collected from buccal cells. We used principal components analysis to compute a summary statistic for CpG sites across candidate genes. The first and second components were used as outcome variables in mixed linear regression analyses with harsh parenting as a predictor variable. We found harsh parenting significantly predicted methylation of several HPA axis genes, including novel gene associations with AVPRB1, CRHR1, CRHR2, and MC2R (FDR corrected p < 0.05). Further, we found NR3C1 methylation predicted a steeper diurnal cortisol slope. Our results extend the current literature by demonstrating harsh parenting may influence DNA methylation similarly to more extreme early life experiences such as abuse and neglect. Further, we show NR3C1 methylation is associated with diurnal HPA function. Elucidating the molecular consequences of harsh parenting on health can inform best parenting practices and provide potential treatment targets for common complex disorders.
2021-04-01 | GSE147058 | GEO
Project description:Environmental cues during gestation could exert transgenerational effects on behavior mainly through changes in epigenetic marks such as DNA methylation. However, the role of histone modifications in the inheritance of acquired phenotypes remains largely unknown in mammals. Here, we report that gestational choline supplementation (GCS) in maternal mice exerts anxiolytic effects on male offspring across 2 generations. Correspondingly, GCS-induced H3K9 hyperacetylation in the Nr3c1 promoter in male hippocampus leads to upregulation of Nr3c1 and its encoded protein, glucocorticoid receptor (GR), across 2 generations through the male germline. Furthermore, inhibition of CREB-binding protein (CBP) histone acetyltransferase (HAT) function restored GCS-induced epigenetic and behavioral alterations, suggesting that CBP function as a HAT to increase Nr3c1 expression through H3K9 hyperacetylation. Thus, GCS-induced GR upregulation through CBP-mediated H3K9 hyperacetylation in the Nr3c1 promoter is associated with anxiolytic behavior in male offspring, highlighting the role of histone modification in acquired phenotypes across mammalian generations.
2021-09-01 | GSE84316 | GEO
Project description:Environmental cues during gestation could exert transgenerational effects on behavior mainly through changes in epigenetic marks such as DNA methylation. However, the role of histone modifications in the inheritance of acquired phenotypes remains largely unknown in mammals. Here, we report that gestational choline supplementation (GCS) in maternal mice exerts anxiolytic effects on male offspring across 2 generations. Correspondingly, GCS-induced H3K9 hyperacetylation in the Nr3c1 promoter in male hippocampus leads to upregulation of Nr3c1 and its encoded protein, glucocorticoid receptor (GR), across 2 generations through the male germline. Furthermore, inhibition of CREB-binding protein (CBP) histone acetyltransferase (HAT) function restored GCS-induced epigenetic and behavioral alterations, suggesting that CBP function as a HAT to increase Nr3c1 expression through H3K9 hyperacetylation. Thus, GCS-induced GR upregulation through CBP-mediated H3K9 hyperacetylation in the Nr3c1 promoter is associated with anxiolytic behavior in male offspring, highlighting the role of histone modification in acquired phenotypes across mammalian generations.
2021-09-01 | GSE84315 | GEO
Project description:Environmental cues during gestation could exert transgenerational effects on behavior mainly through changes in epigenetic marks such as DNA methylation. However, the role of histone modifications in the inheritance of acquired phenotypes remains largely unknown in mammals. Here, we report that gestational choline supplementation (GCS) in maternal mice exerts anxiolytic effects on male offspring across 2 generations. Correspondingly, GCS-induced H3K9 hyperacetylation in the Nr3c1 promoter in male hippocampus leads to upregulation of Nr3c1 and its encoded protein, glucocorticoid receptor (GR), across 2 generations through the male germline. Furthermore, inhibition of CREB-binding protein (CBP) histone acetyltransferase (HAT) function restored GCS-induced epigenetic and behavioral alterations, suggesting that CBP function as a HAT to increase Nr3c1 expression through H3K9 hyperacetylation. Thus, GCS-induced GR upregulation through CBP-mediated H3K9 hyperacetylation in the Nr3c1 promoter is associated with anxiolytic behavior in male offspring, highlighting the role of histone modification in acquired phenotypes across mammalian generations.
2021-09-01 | GSE84314 | GEO