E-GEOD-44934
Ontology highlight
ABSTRACT:
PROVIDER: E-GEOD-44934 | ExpressionAtlas | 2015-07-11
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Pharmacologic Inhibition of Epigenetic Modification Reveals Targets of Aberrant Promoter Methylation in Ewing Sarcoma
| PRJNA192549 | ENA
Project description:Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons (ASEs) and inhibiting DNA methylation results in aberrant splicing of ASEs. The methyl-CpG binding protein MeCP2 is enriched in included ASEs, particularly those that are also highly DNA methylated, and inhibition of DNA methylation disrupts specific targeting of MeCP2 to exons. Interestingly, ablation of MeCP2 results in increased nucleosome acetylation and aberrant skipping events of ASEs. We further show that inhibition of histone deacetylases leads to a highly significant overlap of exon skipping events caused by knocking-down MeCP2. Together, our data indicate that intragenic DNA methylation operates in exon definition to modulate alternative splicing and can enhance exon recognition via recruitment of the multifunctional protein MeCP2, which thereby maintains local histone hypoacetylation through its established interaction with HDACs. MeCP2 ChIP-Seq in IMR90 and HCT116 cells
2013-08-13 | E-GEOD-47677 | biostudies-arrayexpress
Project description:<p>Aberrant DNA methylation changes are known to occur during prostate cancer progression beginning with precursor lesions. Utilizing fifty nanograms of genomic DNA in Methylplex-Next Generation Sequencing (M-NGS) we mapped the global DNA methylation patterns in prostate tissues (n=17) and cells (n=2). Peaks were located from mapped reads obtained in each sequencing run using a Hidden Markov Model (HMM)-based algorithm previously used for Chip-Seq data analysis(<a href="http://www.sph.umich.edu/csg/qin/HPeak">http://www.sph.umich.edu/csg/qin/HPeak</a>). The total methylation events in intergenic/intronic regions between benign adjacent and cancer tissues were comparable. Promoter CGI methylation gradually increased from -12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues and approximately 20% of all CpG islands (CGIs) (68,508) were methylated in tissues. We observed distinct patterns in promoter methylation around transcription start sites, where methylation occurred directly on the CGIs, flanking regions and on CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific and several previously studied targets were among them. A novel cancer specific DMR in WFDC2 promoter showed 77% methylation in cancer (17/22), 100% methylation in transformed prostate cell lines (6/6), none in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested a role for DNA methylation in alternate transcription start site utilization. While methylated promoters containing CGIs had mutually exclusive H3K4me3 modification, the histone mark was absent in CGI sparse promoters. Finally, we observed difference in methylation of LINE-1 elements between transcription factor ERG positive and negative cancers. The comprehensive methylome map presented here will further our understanding of epigenetic regulation of the prostate cancer genome. Overall Design: We mapped the global DNA methylation patterns in prostate tissues (n=17) and cells (n=2) from fifty nanograms of genomic DNA using Methylplex-Next Generation Sequencing (M-NGS). For replicate analysis in cell lines, a total of 4 runs were completed for PrEC prostate normal cell line, and 5 runs were completed for LNCaP prostate cancer cell line. For tissue samples, 2 benign prostate samples were sequenced twice on Illumina next generation sequencing platform to access overall repeatability of M-NGS.</p>
| phs000597 | dbGaP
Project description:Aberrant DNA methylation is induced at specific promoter CpG islands (CGIs) in contrast with mutations. The specificity is influenced by genome architecture and epigenetic factors, but their relationship is still unknown. In this study, we isolated promoter CGIs susceptible and resistant to aberrant methylation induction during prostate and breast carcinogenesis. The effect of genome architecture was more evident for promoter CGIs susceptible in both of the two tissues than for promoter CGIs susceptible only in one tissue. Multivariate analysis of promoter CGIs with tissue-nonspecific susceptibility showed that genome architecture, namely a remote location from SINE (OR=5.98; 95% CI=2.33-15.34) and from LINE (OR=2.08; 95% CI=1.03-4.21), was associated with increased susceptibility, independent of epigenetic factors such as the presence of RNA polymerase II (OR=0.09; 95% CI=0.02-0.48) and H3K27me3 (OR=3.28; 95% CI=1.17-9.21). These results showed that methylation susceptibility of promoter CGIs is determined both by genome architecture and epigenetic factors, independently.
2011-06-06 | GSE28284 | GEO
Project description:Objectives: Earlier studies involving a priori gene selection have identified promoter regions deregulated by DNA methylation changes in oral squamous cell cancers (OSCCs) and precancers. Interrogation of global DNA methylation patterns for such specimens has not been reported, though such analyses are needed to uncover novel molecular factors driving disease. Materials and Methods: We evaluated global DNA methylation patterns for 30 biopsies obtained from 10 patients undergoing surgical removal of an OSCC or carcinoma in situ (CIS). From a disease field in each patient, we collected i) dysplastic, ii) CIS or OSCC, and iii) adjacent normal biopsies. DNA isolated from each biopsy was profiled for methylation status using the Illumina HumanMethylation27K platform. Results: Our data demonstrate that aberrant methylation of promoter CpG islands exists across oral precancer and OSCC genomes. Non-hierarchical clustering of all methylation data revealed distinct methylation patterns between the normal and the CIS/OSCC tissues (with results for dysplastic biopsies split between groups). Multiple genes exhibiting recurrent aberrant DNA methylation were found for both dysplastic and CIS/OSCC groups, and included enrichment for genes found in the WNT and MAPK signaling pathways. Conclusion: In identifying aberrant DNA methylation at the earliest stages of oral precancer and finding recurring epigenetic disruption of specific genes/pathways across our analyzed cohort, we conclude that CpG methylation changes are a hallmark of oral cancer progression and that global DNA methylation analyses are an essential component for wider studies seeking to derive biomarkers or potentially druggable targets for improving oral cancer outcomes. Bisulphite converted DNA from the 30 samples were hybridised to the Illumina Infinium 27k Human Methylation BeadChip v1.2. Total RNA from 30 oral cancer samples were hybridized to Agilent 4x44k gene expression microarray.
2013-09-18 | E-GEOD-46802 | biostudies-arrayexpress
Project description:Genetic and epigenetic alterations are essential for the initiation and progression of human cancer. We previously reported that primary human medulloblastomas showed extensive cancer-specific CpG island DNA hypermethylation in critical developmental pathways. To determine whether genetically engineered mouse models (GEMMs) of medulloblastoma have comparable epigenetic changes, we assessed genome-wide DNA methylation in three mouse models of medulloblastoma. In contrast to human samples, very few loci with cancer-specific DNA hypermethylation were detected, and in almost all cases the degree of methylation was relatively modest compared to the dense hypermethylation in the human cancers. To determine if this finding was common to other GEMMs, we examined a Burkitt lymphoma and breast cancer model and did not detect promoter CpG island DNA hypermethylation, suggesting that human cancers and at least some GEMMs are fundamentally different with respect to this epigenetic modification. These findings provide an opportunity to both better understand the mechanism of aberrant DNA methylation in human cancer and construct better GEMMs to serve as preclinical platforms for therapy development. Examination of DNA methylation in one representative human medulloblastoma patient sample and three different mouse models of medulloblastoma using RRBS
2013-10-10 | E-GEOD-45341 | biostudies-arrayexpress
Project description:Study of promoter methylation of ewing sarcoma cell lines and mesenchymal stem cell from ewing sarcoma patients and healthy donors
2018-10-24 | GSE118872 | GEO
Project description:Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons (ASEs) and inhibiting DNA methylation results in aberrant splicing of ASEs. The methyl-CpG binding protein MeCP2 is enriched in included ASEs, particularly those that are also highly DNA methylated, and inhibition of DNA methylation disrupts specific targeting of MeCP2 to exons. Interestingly, ablation of MeCP2 results in increased nucleosome acetylation and aberrant skipping events of ASEs. We further show that inhibition of histone deacetylases leads to a highly significant overlap of exon skipping events caused by knocking-down MeCP2. Together, our data indicate that intragenic DNA methylation operates in exon definition to modulate alternative splicing and can enhance exon recognition via recruitment of the multifunctional protein MeCP2, which thereby maintains local histone hypoacetylation through its established interaction with HDACs. RNA-Seq in IMR90 and HCT116
2013-08-13 | E-GEOD-47488 | biostudies-arrayexpress
Project description:Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers using a set of specific genes that are regulated by RON/MSP through MBD4-directed aberrant DNA methylation revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent prevents activation of the RON/MBD4 pathway and blocks metastasis of patient-derived breast tumor grafts in vivo. Examination of 3 cell types.
2014-01-02 | E-GEOD-52687 | biostudies-arrayexpress
Project description:Aberrant promoter methylation and gene amplification in colorectal cancer
| PRJNA205527 | ENA