DNA methylation analysis of prostate cancer cell lines and tissues using Next Generation Sequencing
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE27618 | GEO | 2011/05/09
SECONDARY ACCESSION(S): PRJNA141775
REPOSITORIES: GEO
Similar Datasets
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:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. 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). A Hidden Markov Model (HMM)-based algorithm previously used for Chip-Seq data analysis(http://www.sph.umich.edu/csg/qin/HPeak) was used to locate peaks from mapped reads obtained in each sequencing run. The total methylation events in intergenic/intronic regions between benign adjacent and cancer tissues were comparable. While approximately 20% of all CpG islands (CGIs) (68,508) were methylated in tissues, promoter CGI methylation gradually increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues. We found 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. We mapped the global DNA methylation patterns in prostate tissues (n=17; data not available in GEO - being deposited in dbGaP for controlled access) 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 ran twice on illumina next generation sequencing platform to access overall repeatability of M-NGS.
2011-05-09 | E-GEOD-27618 | biostudies-arrayexpress
Project description:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in selected prostate tissues and cell lines using Methylplex-Next Generation Sequencing (M-NGS). Hidden Markov Model based next generation sequence analysis identified ~68,000 methylated regions per sample. While global CpG Island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively. We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific, including numerous novel DMRs. A novel cancer specific DMR in WFDC2 promoter showed heavy methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion positive and negative cancers. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression. Next generation Sequencing for Gene expression using the RNA-Seq methodology from LNCaP and PrEC cell lines
2011-05-09 | E-GEOD-29155 | biostudies-arrayexpress
Project description:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in selected prostate tissues and cell lines using Methylplex-Next Generation Sequencing (M-NGS). Hidden Markov Model based next generation sequence analysis identified ~68,000 methylated regions per sample. While global CpG Island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively. We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific, including numerous novel DMRs. A novel cancer specific DMR in WFDC2 promoter showed heavy methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion positive and negative cancers. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression.
2011-05-09 | GSE29155 | GEO
Project description:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in selected prostate tissues and cell lines using Methylplex-Next Generation Sequencing (M-NGS). Hidden Markov Model based next generation sequence analysis identified ~68,000 methylated regions per sample. While global CpG Island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively. We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific, including numerous novel DMRs. A novel cancer specific DMR in WFDC2 promoter showed heavy methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion positive and negative cancers. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression. This SuperSeries is composed of the SubSeries listed below.
2011-05-03 | GSE27619 | GEO
Project description:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in selected prostate tissues and cell lines using Methylplex-Next Generation Sequencing (M-NGS). Hidden Markov Model based next generation sequence analysis identified ~68,000 methylated regions per sample. While global CpG Island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively. We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific, including numerous novel DMRs. A novel cancer specific DMR in WFDC2 promoter showed heavy methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion positive and negative cancers. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression. In this submission, Agilent expression array data used for Gene Set Enrichment Analysis (GSEA) for enrichment analysis for gene repression is provided.
2011-05-03 | GSE27616 | GEO
Project description:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in selected prostate tissues and cell lines using Methylplex-Next Generation Sequencing (M-NGS). Hidden Markov Model based next generation sequence analysis identified ~68,000 methylated regions per sample. While global CpG Island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively. We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific, including numerous novel DMRs. A novel cancer specific DMR in WFDC2 promoter showed heavy methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion positive and negative cancers. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression. In this data, genes methylated in LNCaP and significantly overexpressed after 5'Azacytidine treatment of LNCaP cells are assessed by Agilent gene expression microarray as a validation for gene repression mechanism due to methylation change.
2010-11-15 | GSE25346 | GEO
Project description:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in selected prostate tissues and cell lines using Methylplex-Next Generation Sequencing (M-NGS). Hidden Markov Model based next generation sequence analysis identified ~68,000 methylated regions per sample. While global CpG Island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively. We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific, including numerous novel DMRs. A novel cancer specific DMR in WFDC2 promoter showed heavy methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion positive and negative cancers. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression. In this data, we are providing Methylplex-PrEC and LNCaP libraries hybridized on Agilent CpG Array, which we chose to perform correlation analysis with deep sequencing result. The LNCaP and PrEC 400bp-5 deep sequencing results were compared with this data and obtained high correlation.
2011-05-03 | GSE27617 | GEO
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.v1.p1 | EGA
Project description:While the majority of RNA polymerase II initiation events in mammalian genomes take place within CpG island (CGI) promoters, our understanding of their regulation remains limited. Here we combine single-molecule footprinting with interaction proteomics to identify BANP as a critical CGI regulator and the long sought-after TF that binds the orphan CGCG element in mouse and human. We show that BANP drives the activity of essential metabolic genes in the mouse genome in pluripotent and terminally differentiated cells. However, BANP binding is strongly repelled by DNA methylation of its motif in vitro and in vivo, which epigenetically restricts most binding to CGIs and accounts for its absence at aberrantly methylated CGIs in cancer cells. Upon binding to an unmethylated motif, BANP opens chromatin and phases nucleosomes. Our results establish Banp as a critical activator and put forth a model whereby CGI promoter activity relies on methylation-sensitive TFs capable of chromatin opening.
2021-06-16 | PXD024794 | Pride