Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA198093 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Inactive or moderately active human promoters are enriched for inter-individual epialleles [Seq]
| PRJNA198092 | ENA
Project description:We first demonstrate that non-genetically determined inter-individual differentially methylated regions (iiDMRs) can be temporally stable for at least two years. Then, we show that iiDMRS are associated with concomitant changes in chromatin state as measured by inter-individual differences in the levels of the histone variant H2A.Z. However, the correlation of promoter iiDMRs with gene expression is negligible and this correlation is not improved even by integrating H2A.Z information. We find that most promoter epialleles, whether genetically or non-genetically determined, are associated with low levels of transcriptional activity, depleted for house keeping genes, and either depleted for H3K4me3/enriched for H3K27me3, or lacking both these marks in human embryonic stem cells. These findings validate in an independent cohort. Interestingly, the key features of iiDMRs are reminiscent of those previously observed for promoters that undergo hyper-methylation in various cancers, in vitro cell culture, and human chronological ageing. DNA Methylation, H2A.z ChIP-seq, RNA-seq (submitted) separately were collected for five normal individuals (samples with "T" prefixes). T21/T22 and T31/T32 are monozygotic twins. Further DNA methylation data was collected from and additional two pairs of MZ twins with technical replication (samples with "C" prefixes - the three digits are pair number, individual number, and replicate number). Bisulphite converted DNA was hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2013-04-22 | E-GEOD-46168 | biostudies-arrayexpress
Project description:We first demonstrate that non-genetically determined inter-individual differentially methylated regions (iiDMRs) can be temporally stable for at least two years. Then, we show that iiDMRS are associated with concomitant changes in chromatin state as measured by inter-individual differences in the levels of the histone variant H2A.Z. However, the correlation of promoter iiDMRs with gene expression is negligible and this correlation is not improved even by integrating H2A.Z information. We find that most promoter epialleles, whether genetically or non-genetically determined, are associated with low levels of transcriptional activity, depleted for house keeping genes, and either depleted for H3K4me3/enriched for H3K27me3, or lacking both these marks in human embryonic stem cells. These findings validate in an independent cohort. Interestingly, the key features of iiDMRs are reminiscent of those previously observed for promoters that undergo hyper-methylation in various cancers, in vitro cell culture, and human chronological ageing. H2A.z ChIP-seq, RNA-seq, and DNA methylation data (submitted separately) were collected for five normal individuals. T21/T22 and T31/T32 are monozygotic twins.
2013-04-22 | E-GEOD-46217 | biostudies-arrayexpress
Project description:We first demonstrate that non-genetically determined inter-individual differentially methylated regions (iiDMRs) can be temporally stable for at least two years. Then, we show that iiDMRS are associated with concomitant changes in chromatin state as measured by inter-individual differences in the levels of the histone variant H2A.Z. However, the correlation of promoter iiDMRs with gene expression is negligible and this correlation is not improved even by integrating H2A.Z information. We find that most promoter epialleles, whether genetically or non-genetically determined, are associated with low levels of transcriptional activity, depleted for house keeping genes, and either depleted for H3K4me3/enriched for H3K27me3, or lacking both these marks in human embryonic stem cells. These findings validate in an independent cohort. Interestingly, the key features of iiDMRs are reminiscent of those previously observed for promoters that undergo hyper-methylation in various cancers, in vitro cell culture, and human chronological ageing.
2013-04-22 | GSE46168 | GEO
Project description:We first demonstrate that non-genetically determined inter-individual differentially methylated regions (iiDMRs) can be temporally stable for at least two years. Then, we show that iiDMRS are associated with concomitant changes in chromatin state as measured by inter-individual differences in the levels of the histone variant H2A.Z. However, the correlation of promoter iiDMRs with gene expression is negligible and this correlation is not improved even by integrating H2A.Z information. We find that most promoter epialleles, whether genetically or non-genetically determined, are associated with low levels of transcriptional activity, depleted for house keeping genes, and either depleted for H3K4me3/enriched for H3K27me3, or lacking both these marks in human embryonic stem cells. These findings validate in an independent cohort. Interestingly, the key features of iiDMRs are reminiscent of those previously observed for promoters that undergo hyper-methylation in various cancers, in vitro cell culture, and human chronological ageing.
2013-04-22 | GSE46217 | GEO
Project description:Graves’ ophthalmopathy (GO) is an extrathyroidal complication of Graves’ hyperthyroidism. Orbital fibroblast, an important cell in the pathogenesis of GO, is responsible for GO characteristics during active and inactive stages; however, information on the extensive profiles and the mechanistic regulations behind orbital fibroblast phenotypes are currently limited. The aim of this study was to compare the proteome profile of orbital fibroblasts isolated from inactive GO, active GO and healthy control. The proteome profile was further integrated with global DNA methylation data to identify this epigenetics regulation involved in the pathogenesis of GO. Methods Orbital fibroblasts culture isolated from five inactive GO, four active GO and five controls were cultured for total protein and DNA extraction. The labelled and fractionated proteins were analyzed with a liquid chromatography tandem-mass spectrometer (LC-MS/MS). On the other hand, the bisulphite-treated DNA was measured with the Illumina Infinium Human Methylation 450K beadchip. Proteome and methylation data were validated by real-time quantitative (RQ)-PCR. Network, pathway and functional analysis were performed by Ingenuity (Qiagen). Results Orbital fibroblasts from active GO displayed overexpression of proteins typically involved with inflammation, cellular proliferation, hyaluronan synthesis and adipogenesis, while several proteins linked to extracellular matrix (ECM) biology and fibrotic disease were overexpressed in orbital fibroblasts from inactive GO. The DNA methylation patterns were similar in healthy control and inactive GO orbital fibroblasts which were distinct from active GO orbital fibroblasts. In orbital fibroblasts from active GO hypermethylated genes link to inflammation while those genes hypomethylated are involved in adipogenesis and autoimmune-related genes. For the network analysis, overlapped between hypermethylated and hypomethylated genes were observed including NF-B, ERK1/2, Alp, RNA polymerase II, Akt and IFNα. In addition, NF-κB, Akt and IFNα were also identified in networks from the differentially expressed proteins. In general, poor correlation between protein expression, DNA methylation and mRNA expression in our study was observed.
2021-01-27 | PXD022257 | Pride
Project description:X chromosome inactivation (XCI) is a dosage compensation mechanism that silences the majority of genes on one X chromosome in each female cell. In order to characterize epigenetic changes that accompany this process, we measured DNA methylation levels in both 45,X Turner syndrome patients, who carry a single active X chromosome (Xa) and normal 46,XX females, who carry one Xa and one inactive X (Xi). Methylated DNA was immunoprecipitated and hybridized to tiling oligonucleotide arrays, generating epigenetic profiles of active and inactive X chromosomes. We observed that XCI is accompanied by changes in DNA methylation specifically at CpG islands. While the majority of CpG islands show increased methylation levels on the Xi, XCI results in reduced methylation at ~20% of CpG islands. Both intra- and inter-genic CpG islands are epigenetically modified, with the biggest increase in methylation occuring at the promoters of genes silenced by XCI. In contrast, genes escaping XCI have low levels of promoter methylation, while genes that undergo polymorphic silencing show intermediate increases in methylation proportionate to their frequency of inactivation. Thus promoter methylation and susceptibility to XCI are correlated. We observed a global correlation between CpG island methylation and the evolutionary age of different X chromosome strata, and that genes escaping XCI show increased methylation within gene bodies. We utilized our epigenetic map to predict both novel genes escaping XCI, and to identify sequence features that may contribute to the XCI process. Finally, as our study included Turner syndrome patients with single X chromosomes of both maternal and paternal origin we searched for parent-of-origin specific methylation differences, but found no evidence to support imprinting on the human X chromosome. Our study provides the first epigenetic profile of active and inactive X chromosomes, giving novel insights into the phenomenon of dosage compensation. Methylated DNA was enriched by immunoprecipitation using antibodies against 5-methylcytosine. meDIP and input DNA was labeled with cy5 and cy3 respectively and hybridized to Nimblegen arrays comprising 2.1 million 50-85mers covering human chromosomes 20, 21, 22, X and Y at a mean density of ~1 probe per 100bp. Resulting log2 fluorescence ratios correspond to methylation levels. Seven patients with Turner syndrome (45,X karyotype), and three normal females (46,XX karyotype) were analyzed. Of the Turner syndrome cases, four had a maternally-derived X, and three had a paternally-derived X chromosome.
2010-07-20 | E-GEOD-22551 | biostudies-arrayexpress
Project description:Genetic loci displaying environmentally responsive epigenetic marks, termed metastable epialleles, offer a solution to the paradox presented by genetically identical yet phenotypically distinct individuals. The murine viable yellow agouti (Avy) locus is a well-described metastable epiallele that serves as a visual epigenetic biosensor. The Avy locus exhibits a high R-value or ratio of inter-individual (Vi) to inter-tissue (Vt) variance in gene expression, characteristic of what we term the ‘Agouti Expression Fingerprint.’ We propose a novel method for identification of candidate metastable epialleles based on the Agouti Expression Fingerprint, defining candidates as loci with R-values greater than 1.5 on expression microarray. Using Expression data from tissues of the three germ layers (liver, kidney, brain), high variance in agouti RNA levels among isogenic animals coupled with low variance among tissue types in individual animals is demonstrated. Here, we provide proof of concept for the ‘Agouti Expression Fingerprint’; the characterization of epigenetically labile loci in humans will be crucial to the development of novel screening and therapeutic targets for human disease prevention. For expression microarray studies, total RNA was isolated from liver, kidney, and brain tissue from 10 male Avy/a mice (2 per each of the 5 coat color classes) at time of weaning and coat color determination (day 22). Using Affymetrix GeneChip Mouse Genome 2.0 arrays (Santa Clara, CA), we queried the entire mouse genome for candidate metastable epialleles that display the Agouti Fingerprint. Approximately 100 of the greater than 40,000 transcripts on the mouse array displayed an expression pattern characterized as high inter-individual variation coupled with low inter-tissue variation (R-value > 1.5).
2011-07-14 | E-GEOD-28559 | biostudies-arrayexpress
Project description:During development and differentiation, enhancers, and not promoters are most dynamic in their DNA methylation status. However, the causal relationship between enhancer activity and methylation is not clear. Here, we describe that during early zebrafish development, enhancer activity has little influence on DNA methylation, and that hypo-methylation is a unique feature of primed enhancers, whereas active enhancers are hyper-methylated. Hypo-methylated enhancers (hypo-enhancers) are enriched close to important transcription factors (TFs) that act later in development, are specifically de-methylated before the maternal-zygotic transition (MZT), and reside in a unique epigenetic environment. Finally, we demonstrate that hypo-enhancers are functionally active and that they are physically associated with the transcriptional start site (TSS) of target-genes, irrespective of target-gene activity. In conclusion, we demonstrate that early development in zebrafish represents a time-window characterized by non-canonical DNA methylation-enhancer relationships, including global DNA hypo-methylation of inactive enhancers and DNA hyper-methylation of active enhancers. DNA methylation profiles of 4 time points during zebrafish early development.
2015-11-09 | E-GEOD-74789 | biostudies-arrayexpress