MeDIP-chip from livers of cloned and not cloned cattle at two stages (perinatal period, adulthood), using anti-methylcytosine antibody.
Ontology highlight
ABSTRACT:
ORGANISM(S): Bos taurus
PROVIDER: GSE73028 | GEO | 2016/12/21
SECONDARY ACCESSION(S): PRJNA296015
REPOSITORIES: GEO
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Project description:To further our understanding of the role of DNA methylation in development, Methylated DNA Immunoprecipitation (MeDIP) was used in conjunction with a NimbleGen promoter plus CpG island array to identify Tissue and Developmental Stage specific Differentially Methylated DNA Regions (T-DMRs and DS-DMRs) on a genome-wide basis. Four tissues (brain, heart, liver, and testis) from C57BL/6J mice were analyzed at three developmental stages (15 day embryo, E15; new born, NB; 12 week adult, AD). Almost 5,000 adult T-DMRs and 10,000 DS-DMRs were identified. Surprisingly, almost all DS-DMRs were tissue specific (i.e., methylated and ummenthylated in one or more non-overlapping tissues), indicating that the vast majority of unique sequence DNA methylation has tissue specificity. Also, many DS-DMRs were methylated at early development stages (E15 and NB) but unmethylated in adult, indicating “demethylation” has a prominent role in tissue differentiation. The pattern of DNA methylation in adult testis was dramatically different from somatic tissues in many aspects, mostly notably with a very strong bias of methylation in non-CpGi (CpG island) promoter regions (94%). Although the majority of T-DMRs and DS-DMRs tended to be in non-CpGi promoter regions, a relatively large number were also located in CpGi in promoter, intra-genic and inter-genic regions (>15% of all CpGi). Gene Ontology analysis of genes with methylation in non-CpGi promoters indicates enrichment of genes related to membrane proteins and G-protein coupled receptors. Our data also suggest regulatory roles of DNA methylation outside of promoter regions and in alternative promoter selection. Overall, our studies indicate that change in DNA methylation during development is a dynamic, widespread and tissue-specific process involving both DNA methylation and demethylation. Comparison of DNA methylation across 3 developmental stages (15 day embryo, newborn, and adult) for four tissues (brain, heart, liver and testis)
2010-12-31 | E-GEOD-21415 | biostudies-arrayexpress
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
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2022-02-16 | PXD021821 | Pride
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2019-07-17 | GSE134362 | GEO
Project description:Perinatal smoke/nicotine exposure alters lung development and causes asthma in exposed offspring, transmitted transgenerationally. The mechanism underlying the transgenerational inheritance of perinatal smoke/nicotine-induced asthma remains unknown, but germline epigenetic modulations may play a role. Using a well-established rat model of perinatal nicotine-induced asthma, we determined the DNA methylation pattern of spermatozoa of F1 rats exposed perinatally to nicotine in F0 gestation. To identify differentially methylated regions (DMRs), reduced representation bisulfite sequencing was performed on spermatozoa of F1 litters. The top regulated gene body and promoter DMRs were tested for lung gene expression levels, and key proteins involved in lung development and repair were determined. The overall CpG methylation in F1 sperms across gene bodies, promoters, 5’UTRs, exons, introns, and 3’UTRs was not affected by nicotine exposure. However, the methylation levels were different between the different genomic regions. 81 CpG sites, 16 gene bodies, and 3 promoter regions were differentially methylated. Gene enrichment analysis of DMRs revealed pathways involved in oxidative stress, nicotine response, alveolar and brain development, and cellular signaling. Among the DMRs, Dio1 and Nmu were the most hypermethylated and hypomethylated genes, respectively. Gene expression analysis showed that the mRNA expression and DNA methylation were incongruous. Key proteins involved in lung development and repair were significantly different (FDR < 0.05) between the nicotine and placebo-treated groups. Our data show that DNA methylation is remodeled in offspring spermatozoa upon perinatal nicotine exposure. These epigenetic alterations may play a role in transgenerational inheritance of perinatal smoke/nicotine induced asthma.
2021-05-17 | GSE173898 | GEO
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2023-07-17 | PXD037264 | Pride
Project description:Backgroud:Epigenetic modifications (especially altered DNA methylation) resulting in altered gene expression may be one reason for development failure or the abnormality of the cloned animals, but the underlying mechanism of the abnormal phenotype in the cloned piglets remains unrevealed. Some cloned piglets in our study showed abnormal phenotypes such as big tongue (longer and thicker), limp, and exomphalos, which is similar to the human BWS syndrome. Here we conducted DNA methylation (DNAm) immunoprecipitation binding high throughput sequencing (MeDIP-seq) and RNA sequencing (RNA-seq) of muscle tissues of cloned piglets to investigate the relationship of abnormal DNAm with gene dysregulation and the unusual phenotypes in cloned piglets. Results:Analysis of the methylomes revealed that abnormal cloned piglets suffered more hypomethylated differentially methylated regions (DMRs) than hypermethylated DMRs compared to the normal cloned piglets. The DNAm level in the CpG Island was higher in the abnormal cloned piglets. Some repetitive elements, such as SINE/tRNA-Glu Satellite/centr also showed significant differences. Besides we detected 1,711 differentially expressed genes (DEGs) between the two groups, of which 243 genes also changed methylation level in the abnormal cloned piglets. The altered DNA methylation mainly affected the low and silent expression genes. We also found some interesting pathways and genes, such as MAPK signalling pathway, hypertrophic cardiomyopathy pathway, TPM3 gene and the imprinted gene PLAGL1, which may played important roles in the abnormal phenotype development. Conclusions;The abnormal cloned piglets showed substantial change both in the DNAm and the gene expression levels. Our data may provide new insights into understanding the molecular mechanisms of the reprogramming of genetic information in cloned animals. We dissected the biceps femoris muscle from the abnormal cloned piglets and the normal cloned piglets, and analyzed the difference of MeDIP-seq and RNA-seq between the two groups. This represents the RNA-Seq study only
2014-09-03 | E-GEOD-51282 | biostudies-arrayexpress
Project description:Backgroud:Epigenetic modifications (especially altered DNA methylation) resulting in altered gene expression may be one reason for development failure or the abnormality of the cloned animals, but the underlying mechanism of the abnormal phenotype in the cloned piglets remains unrevealed. Some cloned piglets in our study showed abnormal phenotypes such as big tongue (longer and thicker), limp, and exomphalos, which is similar to the human BWS syndrome. Here we conducted DNA methylation (DNAm) immunoprecipitation binding high throughput sequencing (MeDIP-seq) and RNA sequencing (RNA-seq) of muscle tissues of cloned piglets to investigate the relationship of abnormal DNAm with gene dysregulation and the unusual phenotypes in cloned piglets. Results:Analysis of the methylomes revealed that abnormal cloned piglets suffered more hypomethylated differentially methylated regions (DMRs) than hypermethylated DMRs compared to the normal cloned piglets. The DNAm level in the CpG Island was higher in the abnormal cloned piglets. Some repetitive elements, such as SINE/tRNA-Glu Satellite/centr also showed significant differences. Besides we detected 1,711 differentially expressed genes (DEGs) between the two groups, of which 243 genes also changed methylation level in the abnormal cloned piglets. The altered DNA methylation mainly affected the low and silent expression genes. We also found some interesting pathways and genes, such as MAPK signalling pathway, hypertrophic cardiomyopathy pathway, TPM3 gene and the imprinted gene PLAGL1, which may played important roles in the abnormal phenotype development. Conclusions;The abnormal cloned piglets showed substantial change both in the DNAm and the gene expression levels. Our data may provide new insights into understanding the molecular mechanisms of the reprogramming of genetic information in cloned animals. We dissected the biceps femoris muscle from the abnormal cloned piglets and the normal cloned piglets, and analyzed the difference of MeDIP-seq and RNA-seq between the two groups.
2014-09-03 | E-GEOD-51476 | biostudies-arrayexpress
Project description:To further our understanding of the role of DNA methylation in development, Methylated DNA Immunoprecipitation (MeDIP) was used in conjunction with a NimbleGen promoter plus CpG island array to identify Tissue and Developmental Stage specific Differentially Methylated DNA Regions (T-DMRs and DS-DMRs) on a genome-wide basis. Four tissues (brain, heart, liver, and testis) from C57BL/6J mice were analyzed at three developmental stages (15 day embryo, E15; new born, NB; 12 week adult, AD). Almost 5,000 adult T-DMRs and 10,000 DS-DMRs were identified. Surprisingly, almost all DS-DMRs were tissue specific (i.e., methylated and ummenthylated in one or more non-overlapping tissues), indicating that the vast majority of unique sequence DNA methylation has tissue specificity. Also, many DS-DMRs were methylated at early development stages (E15 and NB) but unmethylated in adult, indicating “demethylation” has a prominent role in tissue differentiation. The pattern of DNA methylation in adult testis was dramatically different from somatic tissues in many aspects, mostly notably with a very strong bias of methylation in non-CpGi (CpG island) promoter regions (94%). Although the majority of T-DMRs and DS-DMRs tended to be in non-CpGi promoter regions, a relatively large number were also located in CpGi in promoter, intra-genic and inter-genic regions (>15% of all CpGi). Gene Ontology analysis of genes with methylation in non-CpGi promoters indicates enrichment of genes related to membrane proteins and G-protein coupled receptors. Our data also suggest regulatory roles of DNA methylation outside of promoter regions and in alternative promoter selection. Overall, our studies indicate that change in DNA methylation during development is a dynamic, widespread and tissue-specific process involving both DNA methylation and demethylation.
2010-12-31 | GSE21415 | GEO
Project description:Epigenetic reprogramming using demethylating drugs is a promising approach for cancer therapy, but its efficacy is highly dependent on the dosing regimen. Low-dose treatment for a prolonged period shows a high therapeutic efficacy, despite its small demethylating effect. Here, we aimed to reveal the mechanisms of how such low-dose treatment shows high efficacy by focusing on epigenetic reprograming at the single-cell level. Single-cell RNA-sequencing of HCT116 cells treated with decitabine (DAC) revealed that up-regulated genes were highly variable at the single-cell level. To analyze functional consequences at the single-cell level, DAC-treated HCT116 cells were cloned. While only partial reduction of methylation levels was observed in bulk cells, complete demethylation of specific cancer-related genes was observed, depending upon clones. For example, p16 was completely demethylated in the H3-32 clone out of 9 clones, and this clone showed slower proliferation than other clones without demethylation. In addition, in this clone, the fraction of cells with tetraploid became much larger, indicating that cellular senescence was induced. These results showed that epigenetic reprogramming of specific cancer-related pathways at the single-cell level is likely to underlie the high efficacy of low-dose DNA demethylating therapy.
2020-10-02 | GSE149255 | GEO