Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ACCESS DATA

Json Xml

Similar Datasets

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

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.

2012-05-31 | GSE38352 | GEO

Cell type specific transcriptomic alterations in prefrontal deep-layer pyramidal neurons in individuals with a history of childhood abuse

Project description:Childhood abuse significantly increases the lifetime risk of negative mental health outcomes, including psychiatric disorders, such as depression and suicide. While clinical and epidemiological associations are well characterized, the molecular mechanisms through which adverse experiences in early life influence mental health outcomes over the lifespan remain unclear. In this study, we employed laser capture microdissection followed by RNA sequencing (LCM-seq) to investigate transcriptomic alterations to prefrontal deep-layer pyramidal neurons in individuals with a history of childhood abuse (N=24) in comparison to controls (N = 21). We first showed that LCM-seqproduced high-quality transcriptomic data that was strongly enriched for our cell type of interest (95.8% contribution). Differential expression analysis revealed119 genes that were altered between cases versus controls. Using weighted correlation network analysis (WGCNA) we next identified a network of downregulated genes, in individuals with a history of childhood abuse (r = -0.30, p = 0.04), that was enriched in pathways related to nervous system development and plasticity. The eigengene of this network was significantly correlated (r(23) = 0.490, p = 0.021) with average cell body volume of deep-layer pyramidal neurons. Of the 1042 mRNA genes within this network, 81 were differentially expressed between cases and controls. Using high-throughput qPCR, and comparing with an additional group of depressed subjects who died by suicide without a history of childhood abuse (N = 29), we found 7 genes whose expression levels were significantly (p < 0.05) predicted by a history of childhood abuse but not major depressive disorder and suicide.Our study, therefore, advances our understanding of the long term impact of childhood abuse and points to some of the molecular pathways that may underly previously observed alterations innervous system development and plasticity.

2022-12-30 | GSE157197 | GEO

Broad epigenetic signature of maternal care in the brain of adult rats (DNA methylation and H3K9 acetylation profiles)

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

Harsh Parenting Predicts Novel HPA Receptor Gene Methylation and NR3C1 Methylation Predicts Cortisol Daily Slope in Middle Childhood

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

Association of childhood chronic physical aggression with a DNA methylation signature in adult human T cells

Project description:Chronic physical aggression (CPA) is characterized by frequent use of physical aggression from early childhood to adolescence. Observed in approximately 5% of males, it is associated with early childhood adverse environments. DNA methylation, a covalent modification of DNA, regulates genome function and has been associated with early childhood adverse environments. We analyzed T cell DNA genome-wide promoter methylation profiles from two groups of adult males assessed annually for frequency of physical aggression between 6 and 15 years of age: a group with CPA and a control group. Whole genome methylation analysis was performed using MeDIP followed by hybridization to microarrays. We mapped the promoter regions of 20 000 genes and 400 microRNAs. The subjects were recruited from participants in two longitudinal studies of child development9,47. 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 had a history of high physical aggression from age 6 to 15 years (chronic physical aggression group, CPA). The second group was recruited from the same longitudinal studies but included only those who did not have a history of high physical aggression from age 6 to 15 (Control group). A total of 65 eligible subjects agreed to participate (8 CPA and 57 controls). Using custom-designed microarrays with 244K probes tiling the promoter regions of 20000 genes and 400 microRNAs, we obtained DNA methylation profiles by meDIP-chip. Each profile was generated in triplicate.

2013-09-30 | E-GEOD-50674 | biostudies-arrayexpress

Immunological subtypes of depression: insights from monocyte gene expression

Project description:32 genes of a previously established inflammation-related gene signature were assessed in 197 patients with MDD and 151 controls collected during the EU-MOODINFLAME project. Monocyte gene expression data were related to age, gender, BMI, depression severity, Childhood Adversity (CA), and Suicide Risk (SR) data studycenter 1

2020-03-27 | GSE147582 | GEO

Immunological subtypes of depression: insights from monocyte gene expression III

2020-03-27 | GSE147584 | GEO

Immunological subtypes of depression: insights from monocyte gene expression II

2020-03-27 | GSE147583 | GEO

A transcriptomic approach for the evaluation of risk biomarkers in adolescents with a history of a traumatic childhood

Project description:The experience of childhood maltreatment (CM) is highly associated with the occurrence of psychiatric disorders. The impact of CM on neurodevelopmental trajectories is not fully elucidated. Here, we aim to investigate, the impact of different types of CM on the transcriptome expressed by peripheral blood mononuclear cells in adolescence. Adolescents who experienced different types of CM or normal environment were exposed to a comprehensive screening aimed to evaluate psychological and behavioural parameters. Among them, we selected four subpopulations, that experienced respectively Abuse (A), Neglect (N), Abuse and neglect (AN), normal childhood (C). To identify biological markers of their respective experience, mRNA-Seq analysis was performed in PBMC extracted from their blood sampling.

2024-05-15 | GSE255434 | GEO

Genome-wide methylation in alcohol use disorder subjects: implications for an epigenetic regulation of the cortico-limbic glucocorticoid receptors (NR3C1)

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data