Genetics, sex and life experience influence DNA methylation in the mouse
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE106379 | GEO | 2018/10/24
REPOSITORIES: GEO
Similar Datasets
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Examined transcriptomes of 5HT1A wild type offspring with 5HT1A wild type/heterozygous mother or 5HT1A KO offspring with 5HT1A of heterozygous/knock out mother
2013-02-04 | E-GEOD-35838 | biostudies-arrayexpress
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Examined 4 samples: 5HT1A wild type offspring with 5HT1A wild type/heterozygous mother or 5HT1A KO offspring with 5HT1A of heterozygous/knock out mother
2013-02-04 | E-GEOD-35854 | biostudies-arrayexpress
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Comparison of methylation patterns in ventral Dentate Gyrus cells of wild type mice versus 5HT1A receptor knockouts, as well as the effect of the maternal 5HT1A genotype
2013-02-04 | E-GEOD-35815 | biostudies-arrayexpress
Project description:The impact of STAT5 on liver DNA methylation was assessed by performing RRBS analysis on male and female mouse liver with a hepatocyte-specific loss of STAT5a and STAT5b. Extensive changes in CpG-methylation were seen in STAT5-deficient liver, where sex differences were abolished at 88% of ~1,500 sex-differentially methylated regions, largely due to increased DNA methylation upon STAT5 loss. STAT5-dependent CpG-hypomethylation was rarely found at proximal promoters of STAT5-dependent genes. Rather, STAT5 primarily regulated the methylation of distal enhancers, where STAT5 deficiency induced widespread hypermethylation at genomic regions enriched for accessible chromatin, enhancer histone marks (H3K4me1, H3K27ac), STAT5 binding, and DNA motifs for STAT5 and other transcription factors implicated in liver sex differences. Thus, the sex-dependent binding of STAT5 to liver chromatin is closely linked to the sex-dependent demethylation of distal regulatory elements linked to STAT5-dependent genes important for liver sex bias.
2020-12-01 | GSE103886 | GEO
Project description:Maternal obesity impacts the health of offspring, increasing the risk of developing obesity and/or other metabolic dysregulation in childhood or later in life. Using a genome-wide methylation assay, we identified sex-dependent dysregulation of the methylome of CD3+ T-lymphocytes, a cell type that plays an important role in obesity and inflammatory diseases, in newborn offspring of overweight and obese mothers. Furthermore, the differentially methylated loci were targeted to regulatory regions of the genome, in imprinted genes and genes identified from GWAS as being related to type 2 diabetes and obesity.
2020-02-07 | GSE94729 | GEO
Project description:We performed genome-wide DNA methylation analysis of 850,000 CpG sites in women and men with chronic Low Back Pain (LBP) and pain free-controls. T cells were isolated (Discovery Cohort, n=32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified.T cells were isolated (Discovery Cohort, n=32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified. A polygenic DNA methylation score for LBP was generated in both women and men. Validation was performed in an independent cohort (Validation Cohort, n=63) of chronic LBP and healthy controls. Analysis with the Discovery Cohort revealed a total of 2,496 and 419 differentially methylated CpGs in women and men, respectively. The majority of these sites were hypo-methylated in women and enriched in genes with functions in the extracellular matrix, the immune system (i.e. cytokines) or in epigenetic processes. In men, we identified a unique chronic LBP DNA methylation signature characterized by significant enrichment for genes from the major histocompatibility complex. A sex-specific polygenic DNA methylation score was generated to evaluate the pain status of each individual and confirmed in The Validation Cohort using pyrosequencing.
2021-11-10 | GSE162350 | GEO
Project description:Reduced representation bisulfite sequencing was used to explore differentially methylated regions and sites within the amygdala of female rat offspring during earlylife and adulthood, in response to maternal high fat diet exposure. DMRs shared across early life and adulthood included pathways involved in neurodevelopment and genes regulating the DNMT machinery and protein function. To our knowledge, this is the first study to identify persistent genome-wide DNA methylation modifications associated with mHFD exposure in offspring from early life to adulthood.
2020-09-18 | GSE158170 | GEO
Project description:DEHP study Phthalate plasticizers are ubiquitous chemicals linked to several cardiovascular diseases in animal models and in humans. In spite of this, the mechanisms by which phthalate exposures cause adverse cardiac health outcomes are unclear. In particular, whether phthalate exposures during pregnancy interfere with normal developmental programming of the cardiovascular system, and the resulting implications this may have for long-term disease risk, are unknown. Recent studies suggest that the effects of phthalates on metabolic and neurobehavioral outcomes are sex-specific. However, the influence of sex on cardiac susceptibility to phthalate exposures has not been investigated. One mechanism by which developmental exposures may influence long-term health is through altered programming of DNA methylation. In this work, we utilized an established mouse model of human-relevant perinatal exposure and enhanced reduced representation bisulfite sequencing to investigate the long-term effects of diethylhexyl phthalate (DEHP) exposure on DNA methylation in the hearts of adult male and female offspring at 5 months of age (n=5-7 mice per sex and exposure). Perinatal DEHP exposure led to hundreds of sex-specific, differentially methylated cytosines (DMCs) and differentially methylated regions (DMRs) in the heart. Pathway analysis of DMCs revealed enrichment for several pathways in females, including insulin signaling, regulation of histone methylation, and tyrosine phosphatase activity. In males, DMCs were enriched for glucose transport, energy generation, and developmental programs. Notably many sex-specific genes differentially methylated with DEHP exposure in our mouse model were also differentially methylated in published data of heart tissues collected from human heart failure patients. Together these data highlight the potential role for DNA methylation in DEHP-induced cardiac effects, and emphasize the importance of sex as a biological variable in environmental health studies. Lead study Environmental factors play an important role in the etiology of cardiovascular diseases. Cardiovascular diseases exhibit marked sexual dimorphism; however, the sex-specific effects of environmental exposures on cardiac health are incompletely understood. Perinatal and adult exposures to the metal lead (Pb) are linked to several adverse cardiovascular outcomes, but the sex-specific effects of this toxicant on the heart have received little attention. Perinatal environmental exposures can lead to disease through disruption of the normal epigenetic programming that occurs during early development. Using a mouse model of human-relevant perinatal environmental exposure, we investigated the effects of exposure to Pb during gestation and lactation on DNA methylation in the hearts of adult offspring mice (n=6 per sex). Two weeks prior to mating, dams were assigned to control or Pb acetate (32 ppm) water, and exposure continued until offspring were weaned at 3 weeks of age. Enhanced reduced-representation bisulfite sequencing was used to measure DNA methylation in the hearts of offspring at 5 months of age. Although Pb exposure stopped at 3 weeks of age, we discovered hundreds of differentially methylated cytosines (DMCs) and regions (DMRs) in males and females at 5 months of age. DMCs/DMRs and their associated genes were sex-specific, with a small, but statistically significant subset overlapping between sexes. Pathway analysis revealed altered methylation of genes important for cardiac and other tissue development in males, and histone demethylation in females. Together, these data demonstrate that perinatal exposure to Pb induces sex-specific changes in cardiac DNA methylation that are present long after cessation of exposure, and highlight the importance of considering sex in environmental epigenetics and mechanistic toxicology studies.
2020-07-15 | GSE152711 | GEO
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human.
2013-02-04 | GSE35854 | GEO
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human.
2013-02-04 | GSE35838 | GEO