Epigenomic code in atherosusceptible endothelia: epigenomic regulation of HOX transcription factors by oxidative stress
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ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2000
ORGANISM(S): Sus scrofa
SUBMITTER: Peter Davies
PROVIDER: E-MTAB-1930 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole blood DNA methylation was characterized at 5.2 million loci by MeDIP-sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain-sensitivity (pain-DMRs). Nine meta-analysis pain-DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2M-CM-^W10-13). Several pain-DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in brain, and altered expression in skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits. MeDIP-sequencing in 100 individulas using a 2 stage design: paired-end MeDIP-seq in 50 monozygotic twins and single-end MeDIP-seq in 50 unrelated individuals.
2013-12-04 | E-GEOD-52965 | biostudies-arrayexpress
Project description:We report the genome-wide DNA methylation mapping of chicken by methylated DNA immunoprecipitation following by highthroughput sequencing, and the gene expression profile of chicken by RNA-seq. For meDIP-seq, about 17,202,074 to 27,501,760 reads were generated for the tissue and liver tissues of the red jungle fowl and the avian broiler each. We found that compared with the red jungle fowl, DNA methylation in muscle tissue of the avian broiler, showed dramatically decline on a genome-wide scale. Furthermore, the length of the highly methylated regions (HMRs) has become shorter in the avian broiler, which has suffered intense artificial selection. In addition to the global changes in DNA methylation, transcriptome-wide analysis of the two breeds of chicken revealed that the patterns of gene expression in the domestic chicken have undergone a specific bias towards a pattern that is more suited to human-made environments with variable expression in certain gene functions, such as immune response and fatty acid metabolism. Our results demonstrated a potential role of epigenetic modification in animal domestication besides the genetic variations. Examination of whole genome DNA methylation status in liver and muscle of two chicken breeds.
2010-04-02 | E-GEOD-21167 | biostudies-arrayexpress
Project description:We have used a chimeric VEGFR-2 in which the extracellular domain of mouse VEGFR-2 was replaced with the extracellular domain of human CSF-1 receptor. VEGFR-2 was immunoprecipitated with anti-VEGFR-2 antibody from PAE cells ectopically expressing VEGFR-2. The immunoprecipitated proteins were eluted and separated on SDS-PAGE, followed by in-gel chymotrypsin or trypsin digestion. The digested samples were analyzed by nano LC/MS/MS on a Thermo Fisher LTQ Orbitrap XL. The LC-MS/MS data were analyzed using Proteome Discoverer (Thermo Fisher Scientific; Version 1.3.0.339). MS/MS search was carried out using Sequest search algorithm against the sequence of target mouse protein from the UniProtKB database. Search parameters included chymotrypsin as the enzyme with four missed cleavage allowed; methylation at lysine and arginine, phosphorylation of serine, threonine, and tyrosine, alkylation at cysteine, and oxidation of methionine were set as dynamic modifications. Precursor and fragment mass tolerance were set to 5 ppm and 0.8 Da, respectively. The false discovery rate was calculated by enabling the peptide sequence analysis using a decoy database. High confidence peptide identifications were obtained by setting a target false discovery rate threshold of 1% at the peptide level.
2019-11-22 | PXD000520 | Pride
Project description:Purpose: Generate genome-wide methylation profiles of non-small cell lung carcinomas (NSCLC) and their matching lung tissues for detection of hypermethylated and hypomethylated regions present in the tumors. Methods: MethylCapture followed by next-generation sequencing (Illumina GAIIx) of 7 nsclc tumor samples and paired lung tissues in replicated, plus one cell line, 2 fully artificially methylated and 2 fully artificially unmethylated controls. Normalization of methylation reads based on CpG coupling factor–method. Relative methylation scores (rms) in 500bp non-overlapping windows. 90th percentile of rpm (reads per million) values for all 500bp genome-wide windows, with rpm <1.33 were considered. Distributions of 10bp bins rms values within each 500bp genomic region were compared using both one-sided Student’s t-test and one-sided Wilcoxon rank-sum test. Testing was done separately for hypo- and hypermethylation and p-value threshold of 10-18. Results: MethylCap-seq data revealed strong positive correlation between replicate experiments and between paired tumor/lung samples. 14472 differentially methylated regions (DMR) with non-overlapping 500 bp windows were found. 57 DMRs were present in all NSCLC tumors. 287 were unique for squamous-cell carcinomas and 26 unique for adenocarcinomas. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. Conclusion: We provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC. The DMRs can be in further studies to develop sensitive biological markers for NSCLC, which may enable non-invasive diagnosis and early detection of the disease, and potentially allow histological classification. MethylCap-seq of 7 nsclc tumor samples and paired lung tissues, plus 2 fully methylated and 2 fully unmethylated controls.
2012-10-05 | E-GEOD-41343 | biostudies-arrayexpress
Project description:Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive lung disease that affects more than 5 million people worldwide with a steady increase in both incidence and mortality. There is currently no effective therapy and the median survival without transplant is 2-5 years. The etiological factor is unknown, but several observational and pathogenesis studies suggest that environmental agents may cause IPF. DNA methylation is a type of chemical modification of DNA such environmental and occupational factors, that can induced a changes in the regulation of biological processes and link to diseases such as a cancer. We hypothesize that the global changes in methylation patterns of IPF lungs caused by environmental factors. In this study we will identify the global methylation signatures of the IPF lung and to compare to methylation signature of lung cancer. The DNA methylation profiles of IPF lung tissue differs from control lung but it shares great similarity with that of lung cancer. Immunoprecipitated methylated DNA from 12 IPF lungs, 10 lung adenocarcinomas and 10 normal histology lungs obtained from the same group of adenocarcinoma patients was hybridized to Agilent human CpG Islands Microarrays. Only probes with a hybridization Tm value between 79 C and 93C were included in the analysis because these show higher quality signal. All probes were divided according to their Tm into 14 groups/bins differing by 1C. Probe signals in each bin were standardized to have an average of 0 and a standard deviation of 1. To work in a CpG island oriented manner, we scored each island for its likelihood to be methylated. For that purpose, each probe was mapped to the genome and the signals of the probes that were mapped to a single CpG island were averaged to obtain the islandM-bM-^@M-^Ys methylation score. Data analysis was performed using BRB-Array Tools and DAVID Bioinformatics Resources software packages.
2012-04-18 | E-GEOD-29895 | biostudies-arrayexpress
Project description:Background Urothelial carcinoma of the bladder (UC) is a common malignancy. Although extensive transcriptome analysis has provided insights into the gene expression patterns of this tumor type, the mechanistic underpinnings of differential methylation remain poorly understood. Multi-level genomic data may be used to profile the regulatory potential and landscape of differential methylation in cancer and gain understanding of the processes underlying epigenetic and phenotypic characteristics of tumors. Methods We perform genome-wide DNA methylation profiling of 98 gene-expression subtyped tumors to identify between-tumor differentially methylated regions (DMRs). We integrate multi-level publically available genomic data generated by the ENCODE consortium to characterize the regulatory potential of UC DMRs. Results We identify 5,453 between-tumor DMRs and derive four DNA methylation subgroups of UC with distinct associations to clinicopathological features and gene expression subtypes. We characterize three distinct patterns of differential methylation and use ENCODE data to show that tumor subgroup-defining DMRs display differential chromatin state, and regulatory factor binding preferences. Finally, we characterize an epigenetic switch involving the HOXA-genes with associations to tumor differentiation states and patient prognosis. Conclusions Genome-wide DMR methylation patterns are reflected in the gene expression subtypes of UC. UC DMRs display three distinct methylation patterns, each associated with intrinsic features of the genome and differential regulatory factor binding preferences. Epigenetic inactivation of HOX-genes correlates with tumor differentiation states and may present an actionable epigenetic alteration in UC. MeDIP hybridizations on 98 human urothelial carcinoma samples and 4 normal urothelium samples on Nimblegen 3x720K RefSeq Promoter and CGI aCGH arrays.
2015-05-28 | E-GEOD-58256 | biostudies-arrayexpress
Project description:The experiment was designed to discover deferentially methylated regions between DNA extracted from breast cancer tissues and DNA samples extracted from tissue obtained form breast reduction surgeries. The study involved 20 breast cancer samples and 5 tissue samples from breast reductions. Each of the samples was processed by the arrays and collected data were used to compare the genome wide methylation pattern cancer samples (cases) and breast reduction samples (controls). The methylation pattern of 5 DNA samples from breast reduction was compared with the methylation pattern of 20 DNA samples from breast cancer tumors
2012-12-22 | E-GEOD-43095 | biostudies-arrayexpress
Project description:To gain insights into the function of DNA methylation and its impact on gene expression, we measured methylation in 19,530 mouse promoters and CpG islands. Keywords: DNA methylation, MeDIP The chosen array from NIMBLEGEN (2007-02-27_MM8_ CpG island _ promoter array) represents putative mouse promoters plus CpG islands, each covered by oligonucleotide probes spanning 1.3 kb upstream and 0.5 kb downstream of the transcription start site.
2009-07-30 | E-GEOD-12301 | biostudies-arrayexpress
Project description:Here we used Illumina NGS for high-throughput profiling of the DNA methylome(ERRBS) and hydroxymethylome(hMe-Seal) of primary tumor samples with Acute Myeloid Leukemia(AML). The data can be used to compare hydroxymethylation and methylation patterns from different AML subtypes and normal bone marrow samples. We have sequenced 4 subtypes of AML with hydroxymethylation decrease and 1 subtype with no decrease. We have sequenced 2-5 primary tumor samples for each subtype, and comprated the epigenomic profiles ( ERRBS and hMe-Seal ) of hydroxymethylation deficient subtypes to the control subtype and normal bone marrow samples.
2014-11-20 | E-GEOD-52945 | biostudies-arrayexpress
Project description:DNA methylation was measured by MBD2 enrichment of DNA fragments in IMR90. A statistical model was developed to estimate absolute methylation levels, and compared to whole genome bisulfite sequencing results (Lister, R. et al. (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature) Two techincal replicates of MBD2 methylated DNA enrichment in IMR90 cells.
2012-11-30 | E-GEOD-38679 | biostudies-arrayexpress