Genome-wide maps of DNA methylation state in 2-week rat IUGR islets
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA636838 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11910000.fastq.gz | Fastqsanger.gz | |||
| SRR11910001.fastq.gz | Fastqsanger.gz | |||
| SRR11910002.fastq.gz | Fastqsanger.gz | |||
| SRR11910003.fastq.gz | Fastqsanger.gz | |||
| SRR11910004.fastq.gz | Fastqsanger.gz |
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Project description:Intrauterine growth restriction (IUGR) increases the risk of developing type 2 diabetes in adulthood. A rat model of IUGR induced by bilateral uterine artery ligation at day 18 of gestation, which reduces the blood supply and critical substrates to the fetus, was used to assess the alterations of genome-wide DNA methylation in IUGR islets. At 2 weeks of age, pancreatic islets were isolated and genomic DNA were extracted for TruSeq-HELP tagging assay. Cytosine methylation was compared in the study.
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Project description:Intrauterine growth restriction (IUGR) increases the risk of developing type 2 diabetes in adulthood. A rat model of IUGR induced by bilateral uterine artery ligation at day 18 of gestation, which reduces the blood supply and critical substrates to the fetus, was used to assess the alterations of genome-wide histone modifications in IUGR islets. At 2 and 10 weeks of age, pancreatic islets were isolated and chromatins were extracted for ChIP-Seq study. Chromatin state of H3K4me3, H3K27me3, and H3K27Ac modifications was compared in the study.
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Project description:IUGR is a common complication of pregnancy. We have created a rat model of IUGR which mimics placental insufficiency. Surgery is performed at embryonic day 18 and dams are allowed to deleiver spontaneously. At postnatal day 14, we isolate pancreatic islets and have compared their gene expression with that of control (sham) surgery animals. Two-condition experiment, control vs IUGR pancreatic islets. Biological replicates: 4 control replicates, 4 IUGR replicates.
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Project description:Intrauterine growth restriction (IUGR) increases susceptibility to age-related diseases including type 2 diabetes (T2DM), and is associated with permanent and progressive changes in gene expression and epigenetic regulation. We studied cytosine methylation throughout the genome in pancreatic islets from a rat model of uteroplacental insufficiency, providing a novel and detailed assessment of the genomic distribution and locus-specific patterns of DNA methylation in normal islets as well as the changes that occur as a consequence of IUGR. Utilizing a high throughput approach to study DNA methylation at almost 1 million unique sites throughout the genome, we found ~1,400 changes in methylation (IUGR compared to control) with an estimated false discovery rate of 4.2%. These epigenetic differences were observed in IUGR male rats at 7 weeks of age, preceding the development of diabetes in this model. Therefore, these epigenetic differences represent candidates for mediating the pathogenesis of metabolic disease that occurs later in life in these animals. Moreover, many of the changes we identify are located near genes that regulate processes known to be abnormal in IUGR islets, such as vascularization, β-cell proliferation, insulin secretion, and cell death. Consistent changes in mRNA expression were identified at some of the epigenetically-dysregulated genes including Fgfr1, Gch1, Pcsk5, and Vgf. Globally, epigenetic dysregulation occurred preferentially at conserved intergenic sequences, which are candidate cis-regulatory elements driving differential expression of nearby genes. These results provide insights into the complex developmental consequences of IUGR, and suggest that changes in DNA methylation could mediate a constellation of changes in both gene expression and pancreatic islet development and function, with relevance to T2DM. Direct comparison of DNA methylation in 8 samples consisting of isolated, pooled pancreatic islets from 7-week-old male offspring belonging to 4 IUGR and 4 control litters (Sprague-Dawley rats). Each microarray consists of a two-color comparison of a methylation-sensitive representation of the genome (HpaII) with an internal methylation-insensitive control/reference (MspI).
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Project description:Intrauterine growth restriction is a common complication of pregnancy. We induce IUGR in rats by bilateral uterine artery ligation at e18 of a 23 day gestation. This mimics placental insufficiency. This array experiment compares gene expression changes in isolated pancreatic islets from e19, 24 hours post-surgery , or sham operated animals. RNA from isolated pancreatic islets from e19 fetuses, pooled from an entire litter. There are 4 control (sham) operated litters and 4 IUGR litters.
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