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

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Matthew Suderman

PROVIDER: E-GEOD-20714 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Broad epigenetic signature of maternal care in the brain of adult rats (expression)

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

Broad epigenetic signature of maternal care in the brain of adult rats

Project description:This SuperSeries is composed of the following subset Series: GSE20714: Broad epigenetic signature of maternal care in the brain of adult rats (DNA methylation and H3K9 acetylation profiles) GSE20717: Broad epigenetic signature of maternal care in the brain of adult rats (expression) Refer to individual Series

2011-03-09 | E-GEOD-20840 | biostudies-arrayexpress

Broad epigenetic signature of maternal care in the brain of adult rats (expression)

2011-03-09 | GSE20717 | GEO

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

2011-03-09 | GSE20714 | GEO

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. 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.

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The knockdown of maternal glucocorticoid receptor mRNA alters embryo development in zebrafish

Project description:In zebrafish, ovulated oocytes contain both cortisol deposited from the maternal circulation and maternal mRNA for the glucocorticoid receptor (gr mRNA), which is spread as granular structures throughout the central ooplasm. At the 1-cell stage (0.2 hpf), this transcript is relocated by streamers in the blastodisc area and equally partitioned among blastomeres. At 15 hpf, it is replaced by the zygotic transcript. Morpholino knockdown was applied to block translation (grATG1MO or MO2-nr3c1 and grATG2MO or MO3-nr3c1) of both maternal and zygotic gr transcripts, while a missplicing morpholino (grmismMO or MO4-nr3c1) was used to block post-transcriptionally the zygotic transcript alone. MO2-nr3c1 and MO3-nr3c1 (but not MO4-nr3c1) treatment produced craniofacial and caudal malformations in 1-dpf embryos and 5-dpf larvae, which were also affected by pericardial oedema, persistent yolk sac, reduced subintestinal veins, altered neurogenesis and uninflated swim bladder. Such effects were rescued with trout gr2 mRNA. Pangenomic microarray analysis revealed that 114 and 37 highly expressed transcripts were up- and down-regulated, respectively, by maternal GR protein deficiency in 5-hpf embryos. Similar alterations were found at 10 hpf. These effects were confirmed by real-time PCR of 2 up- (casp8, grp1 and igf2a) and 1 down-regulated transcripts (mcm6) evaluated at 4, 8 and 12 hpf. As the contents of transcripts were modified already at 4 hpf, it seems that the lack of GR affects both ways the molecular machinery for the degradation of maternal mRNAs. These results indicate that the maternal gr transcript participates in the maternal programming of zebrafish development. MO2-nr3c1 morphants were compared with MO2-nr3c1-5m morphants at 5 hpf and 10 hpf. MO2-nr3c1 morphants were compared with wild type (WT) at 5 hpf and 10 hpf. MO2-nr3c1 is a morpholino selected to knockdown translation of gr mRNA. MO2-nr3c1-5m is a specific control morpholino.

2011-11-16 | E-GEOD-25517 | biostudies-arrayexpress

Epigenetic analysis of psychosocial stress among mother-newborn dyads in the Democratic Republic of Congo (EAA)

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Epigenetic analysis of psychosocial stress among mother-newborn dyads in the Democratic Republic of Congo (EWA reanalysis)

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Transcriptomics of rat born to dams fed a diet deficient in methyl group donors

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2023-03-01 | E-MTAB-12728 | biostudies-arrayexpress

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