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GSE69713
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
DNA methylation is an important epigenetic control mechanism that has been shown to be associated with gene silencing through the course of development, maturation and aging. However, only limited data are available regarding the relationship between methylation and gene expression in human development. We analyzed the methylomes and transcriptomes of three human fetal liver samples (gestational age 20-22 weeks) and three adult human liver samples. Genes whose expression differed between fetal and adult numbered 7,673. Adult overexpression was associated with metabolic pathways and, in particular, cytochrome P450 enzymes, while fetal overexpression reflected enrichment for DNA replication and repair. Analysis for DNA methylation using the Illumina Infinium 450K HumanMethylation BeadChip showed that 42% of the quality filtered 426,154 methylation sites differed significantly between adult and fetal tissue (q0.05). Differences were small; 69% of the significant sites differed in their mean methylation beta value by 0.2. There was a trend among all sites toward higher methylation in the adult samples with the most frequent difference in beta being 0.1. Characterization of the relationship between methylation and expression revealed a clear difference between fetus and adult. Methylation of genes overexpressed in fetal liver showed the same pattern as seen for genes that were similarly expressed in fetal and adult liver. In contrast, adult overexpressed genes showed fetal hypermethylation that differed from the similarly expressed genes. An examination of gene region-specific methylation showed that sites proximal to the transcription start site or within the first exon with a significant fetal-adult difference in beta (>0.2) showed an inverse relationship with gene expression. Nearly half of the CpGs in human liver show a significant difference in methylation comparing fetal and adult samples. Sites proximal to the transcription start site or within the first exon that show a transition from hypermethylation in the fetus to hypomethylation or intermediate methylation in the adult are associated with inverse changes in gene expression. In contrast, increases in methylation going from fetal to adult are not associated with fetal-to-adult decreased expression. These findings indicate fundamentally different roles for and/or regulation of DNA methylation in human fetal and adult liver.
Publication Title
Patterns of gene expression and DNA methylation in human fetal and adult liver.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 77 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Current human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat.
Publication Title
Sperm mRNA transcripts are indicators of sub-chronic low dose testicular injury in the Fischer 344 rat.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The goal of this study was to determine the effects of a well-characterized anti-androgen, abiraterone acetate, and a suspected human anti-androgen, di-n-butyl phthalate (DBP) on the androgenic function of human fetal testis. Human fetal testis was xenografted into the renal subcapsular space of castrated male athymic nude mice. Hosts were treated with hCG to stimulate testosterone production in the xenografts, and were concurrently treated with either abiraterone acetate or DBP. While abiraterone acetate (14 d, 75 mg/kg/d p.o.) dramatically reduced testosterone and the weights of androgen-sensitive host organs, DBP (14 d, 500 mg/kg/d p.o.) had no effect on androgenic endpoints.
Publication Title
Differential response to abiraterone acetate and di-n-butyl phthalate in an androgen-sensitive human fetal testis xenograft bioassay.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We have replaced the right arm of chromosome IX in Saccharomyces cerevisiae with a synthetic version to generate synIXR haploids. The synthetic chromosome features multiple sequeunce modifications.
Publication Title
Synthetic chromosome arms function in yeast and generate phenotypic diversity by design.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood. In the present study, we explored transcriptomics and epigenetic differences in the small intestine and colon of prepubescent male and female mice. In addition, the microbiota composition of the colonic luminal content has been examined. At postnatal day 14, male and female C57BL/6 mice were sacrificed and the small intestine, colon and content of luminal colon were isolated. Gene expression of both segments of the intestine was analysed by microarray analysis. DNA methylation of the promoter regions of selected sexually dimorphic genes was examined by pyrosequencing. Composition of the microbiota was explored by deep sequencing. Sexually dimorphic genes were observed in both segments of the intestine of 2-week-old mouse pups, with a stronger effect in the small intestine. Amongst the total of 349 genes displaying a sexually dimorphic effect in the small intestine and/or colon, several candidates exhibited a previously established function in the intestine (i.e. Nts, Nucb2, Alox5ap and Retnl). In addition, differential expression of genes linked to intestinal bowel disease (i.e. Ccr3, Ccl11 and Tnfr) and colorectal cancer development (i.e. Wt1 and Mmp25) was observed between males and females. Amongst the genes displaying significant sexually dimorphic expression, nine genes were histone-modifying enzymes, suggesting that epigenetic mechanisms might be a potential underlying regulatory mechanism. However, our results reveal no significant changes in DNA methylation of analysed CpGs within the selected differentially expressed genes. With respect to the bacterial community composition in the colon, a dominant effect of litter origin was found but no significant sex effect was detected. However, a sex effect on the dominance of specific taxa was observed. This study reveals molecular dissimilarities between males and females in the small intestine and colon of prepubescent mice, which might underlie differences in physiological functioning and in disease predisposition in the two sexes.
Publication Title
Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
During the last few decades, the long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident, but the effects of maternal nutrition on the developing intestine are currently still relatively underexplored. In this study, we investigated in mice the effects of a maternal Western-style (WS) high fat/cholesterol diet, given during the perinatal period, on gene expression and microbiota composition of two-week-old offspring. Microarray analysis revealed that a perinatal WS diet caused significant changes in gene expression in the small intestine and colon of the suckling offspring. A strong sexually dimorphic effect was observed in the affected genes. However, pathway analysis of the differentially expressed genes displayed that in both sexes metabolic and immune functions were strongly affected. Integration of the microbiota and gene expression data applying a multivariate correlation analyses revealed that Bacteroidaceae, Porphyromonadaceae and Lachnospiraceae were the bacterial families that most strongly correlated with gene expression in the colon and not with the bacterial families displaying the most pronounced change due to perinatal exposure to a WS diet. Amongst the genes demonstrating a strong correlation with one or more bacterial families were genes of key importance for intestinal development or functioning (i.e., Pitx2 and Ace2). In conclusion, our data demonstrate a strong programming effect of a maternal WS diet on the development of the intestine in the offspring.
Publication Title
Maternal exposure to a Western-style diet causes differences in intestinal microbiota composition and gene expression of suckling mouse pups.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The hst3hst4 strain (FY background) has the HST3 and HST4 genes, encoding putative NAD-dependent deacetylases that regulate histone 3 K56 acetylation, deleted. Expression profiling using Affymetrix microarrays was used to assess the change in the gene expression in this strain in comparison to wild-type under normal growth conditions.
Publication Title
Histone H3 K56 hyperacetylation perturbs replisomes and causes DNA damage.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Fatty acids comprise the primary energy source for the heart and are mainly taken up via hydrolysis of circulating triglyceride-rich lipoproteins. While most of the fatty acids entering the cardiomyocyte are oxidized, a small portion is involved in altering gene transcription to modulate cardiometabolic functions. So far, no in vivo model has been developed enabling study of the transcriptional effects of specific fatty acids in the intact heart. In the present study, mice were given a single oral dose of synthetic triglycerides composed of one single fatty acid. Hearts were collected 6h thereafter and used for whole genome gene expression profiling. Experiments were conducted in wild-type and PPAR/ mice to allow exploration of the specific contribution of PPAR. It was found that: 1) linolenic acid (C18:3) had the most pronounced effect on cardiac gene expression. 2) The largest similarity in gene regulation was observed between linoleic acid (C18:2) and C18:3. Large similarity was also observed between the synthetic PPAR agonist Wy14643 and docosahexaenoic acid (C22:6). 3) Many genes were regulated by one particular treatment only. Genes regulated by one particular treatment showed large functional divergence. 4) The majority of genes responding to fatty acid treatment were regulated in a PPAR-dependent manner, emphasizing the importance of PPAR in mediating transcriptional regulation by fatty acids in the heart. 5) Several genes were robustly regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g. Acot1, Angptl4, Ucp3). 6) Deletion and activation of PPAR had a major effect on expression of numerous genes involved in metabolism and immunity. Our analysis demonstrates the marked impact of dietary fatty acids on gene regulation in the heart via PPAR.
Publication Title
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sample Metadata Fields
Sex, Treatment
View Samples