Genome-wide DNA methylation analysis using MethylCap-seq in canine diffuse large B-cell (cDLBCL) cell lines
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ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE149925 | GEO | 2020/10/22
REPOSITORIES: GEO
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Project description:We carried out a genome-wide cfDNA methylation profiling study of pancreatic ductal adenocarcinoma (PDAC) patients by Methylated DNA Immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Compared with healthy individuals, 775 differentially methylated regions (DMRs) located in promoter regions were identified in PDAC patients with 761 hypermethylated and 14 hypomethylated regions; meanwhile, 761 DMRs in CpG islands (CGIs) were identified in PDAC patients with 734 hypermethylated and 27 hypomethylated regions (p-value < 35 0.0001). 143 hypermethylated DMRs were further selected which were located in promoter regions and completely overlapped with CGIs. A total of 8 probes from 8 genes were found to fairly distinguish PDAC patients from the healthy individuals, including TRIM73, FAM150A, EPB41L3, SIX3, MIR663, MAPT, LOC100128977 and LOC100130148.
2020-10-29 | E-MTAB-9678 | biostudies-arrayexpress
Project description:DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness. DNA methylome analysis of pooled Human, Chimpanzee and Macaque
2014-02-01 | E-GEOD-48942 | biostudies-arrayexpress
Project description:DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness.
2014-02-01 | GSE48942 | GEO
Project description:Integration of the bacterial T-DNA into the plant genome by virulent agrobacteria causes crown gall development on many plant species. Plant tumor development shares fundamental similarities with mammalian cancer progression despite obvious differences in initiation of tumor development. For neoplastic growth in mammals, DNA methylation changes are known to be essential. The role of epigenetic modifications for plant tumor development is addressed here. Genome-wide comparison of methylation profiles of Arabidopsis crown galls and tumor-free tissue revealed 2,876 annotated genes that were affected by differential methylation. Thereof, 1,822 genes were hit by hypermethylated regions and 1,100 genes overlapped with hypomethylated regions (sum of hyper-and hypomethylated genes is higher than the number of affected genes because one gene may contain several differentially methylated regions [DMRs]). DMRs found to be methylated only in tumor-free tissue covered 275 kb of the genome, whereas those methylated only in crown galls total to 560 kb. Contrary to the globally hypermethylated tumor genome, promoter regions of protein coding genes appeared to be rather hypomethylated. In contrast, mammalian cancer cells are associated with global hypomethylation and local hypermethylation of gene promoters. In summary, while aberrant DNA methylation in mammals increases malignacy of the cancer phenotype, our results indicate that methylation events in the plant genome rather confine tumor growth. All 15,431 mCIP-enriched regions reported in the paper are contained in the supplementary BED files. mCIP of gDNA from crown galls vs. mCIP of gDNA from inflorescence stalks (3 biol. replicates each)
2013-02-18 | E-GEOD-37680 | biostudies-arrayexpress
Project description:To identify Differentially methylated regions (DMRs) in TNBCs, we performed methyl binding domain protein 2 enrichment of DNA followed by massively parallel sequencing (MBD-seq) using 10 breast tumors and 10 matched normal samples for each of the four subtypes (LumA, LumB, HER2, and TNBC), classified according to ER, PR, and HER2 expression. ~~. 468 genes were significantly hypomethylated and 353 genes were significantly hypermethylated in promoter and CDS regions in only TNBC.
2023-06-30 | GSE116877 | GEO
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:Our previous research demonstrated that caffeine exposure on embryonic day (E) 8.5 increased body weight, altered cardiac morphology and function in adult male mice. However, these adverse effects were not observed in adenosine A1 receptor knockout (A1AR-/-) mice. Our hypothesis is that A1AR action mediates changes in DNA methylation patterns in mice exposed in utero to caffeine and that these changes in methylation lead to long-term effects in adult mice. To test this hypothesis, DNA Methylation 2.1M Deluxe Promoter Arrays (NimbleGen) were used to examine the methylation patterns of DNA isolated from adult left ventricles of the A1AR knockout line exposed to 20 mg/kg caffeine at E8.5 in utero. In A1AR+/+ mice, 4,896 hypermethylated and 2,823 hypomethylated regions were discovered in the left ventricles of the caffeine group compared to the normal saline group. In A1AR-/- mice, 1,024 hypermethylated and 1,757 hypomethylated regions were found in the caffeine group. The differentially methylated regions (DMRs) in the caffeine treated A1AR+/+ hearts mapped to 6,148 genes, 4,853 promoters, 4,111 primary transcripts, 816 CpG islands, and 98 miRNAs. Functional annotation clustering of genes revealed that many genes were involved in the development of hypertrophic cardiomyopathy and other heart diseases, which may explain our earlier findings of thickening of the left ventricular wall after in utero caffeine treatment. The methylation changes in several DMRs, mef2c, ins2, tnnt2, and myh6, were validated by bisulfite sequencing. In summary, in utero caffeine exposure caused DNA methylation changes in adult left ventricles and that these changes may be mediated by A1ARs. Pregnant mice were injected at embryonic day 8.5 with 0.9% NaCl (vehicle) or 20 mg/kg caffeine in vehicle i.p. Pups were born and raised until 8-10 weeks of age. Analysis was performed on the following groups vehicle A1AR+/+ (veh+/+), vehicle A1AR-/- (veh-/-), caffeine A1AR+/+ (caff+/+), and caffeine A1AR-/- (caff-/-). Genomic DNA from left ventricles of adult male mice was used. Two biological replicates were measured for each group.
2015-12-19 | E-GEOD-43030 | biostudies-arrayexpress
Project description:Integration of the bacterial T-DNA into the plant genome by virulent agrobacteria causes crown gall development on many plant species. Plant tumor development shares fundamental similarities with mammalian cancer progression despite obvious differences in initiation of tumor development. For neoplastic growth in mammals, DNA methylation changes are known to be essential. The role of epigenetic modifications for plant tumor development is addressed here. Genome-wide comparison of methylation profiles of Arabidopsis crown galls and tumor-free tissue revealed 2,876 annotated genes that were affected by differential methylation. Thereof, 1,822 genes were hit by hypermethylated regions and 1,100 genes overlapped with hypomethylated regions (sum of hyper-and hypomethylated genes is higher than the number of affected genes because one gene may contain several differentially methylated regions [DMRs]). DMRs found to be methylated only in tumor-free tissue covered 275 kb of the genome, whereas those methylated only in crown galls total to 560 kb. Contrary to the globally hypermethylated tumor genome, promoter regions of protein coding genes appeared to be rather hypomethylated. In contrast, mammalian cancer cells are associated with global hypomethylation and local hypermethylation of gene promoters. In summary, while aberrant DNA methylation in mammals increases malignacy of the cancer phenotype, our results indicate that methylation events in the plant genome rather confine tumor growth. All 15,431 mCIP-enriched regions reported in the paper are contained in the supplementary BED files.
2013-02-18 | GSE37680 | GEO
Project description:Our previous research demonstrated that caffeine exposure on embryonic day (E) 8.5 increased body weight, altered cardiac morphology and function in adult male mice. However, these adverse effects were not observed in adenosine A1 receptor knockout (A1AR-/-) mice. Our hypothesis is that A1AR action mediates changes in DNA methylation patterns in mice exposed in utero to caffeine and that these changes in methylation lead to long-term effects in adult mice. To test this hypothesis, DNA Methylation 2.1M Deluxe Promoter Arrays (NimbleGen) were used to examine the methylation patterns of DNA isolated from adult left ventricles of the A1AR knockout line exposed to 20 mg/kg caffeine at E8.5 in utero. In A1AR+/+ mice, 4,896 hypermethylated and 2,823 hypomethylated regions were discovered in the left ventricles of the caffeine group compared to the normal saline group. In A1AR-/- mice, 1,024 hypermethylated and 1,757 hypomethylated regions were found in the caffeine group. The differentially methylated regions (DMRs) in the caffeine treated A1AR+/+ hearts mapped to 6,148 genes, 4,853 promoters, 4,111 primary transcripts, 816 CpG islands, and 98 miRNAs. Functional annotation clustering of genes revealed that many genes were involved in the development of hypertrophic cardiomyopathy and other heart diseases, which may explain our earlier findings of thickening of the left ventricular wall after in utero caffeine treatment. The methylation changes in several DMRs, mef2c, ins2, tnnt2, and myh6, were validated by bisulfite sequencing. In summary, in utero caffeine exposure caused DNA methylation changes in adult left ventricles and that these changes may be mediated by A1ARs.
2015-12-19 | GSE43030 | GEO
Project description:In order to obtain genome-wide profiles, base-resolution methylomes of oocytes and zygotes were generated using the bisulfite sequencing (BS-seq) method for small samples. We find that global loss of DNA methylation during zygotic development in HFD mice. A total of 412 DMRs were identified, of which 294 were hypomethylated (hypo-DMRs; 71.4%) and 118 were hypermethylated (hyper-DMRs; 28.6%) (Fig. 6A and 6B), showing a predominance of hypo-DMRs. Furthermore, we show that hyper-DMRs are significantly depleted from CGI, but enriched in short interspersed elements (SINEs) and non-CGI regions. Strikingly, hypo-DMRs are specifically depleted from SINEs, with a concurrent enrichment in DNA transposons.
2018-11-22 | GSE122829 | GEO