Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences
<p>Abstract</p> <p>Background</p> <p>DNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for en...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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BMC
2011-06-01
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| Series: | BMC Genomics |
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| Online Access: | http://www.biomedcentral.com/1471-2164/12/313 |
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| author | De Marzo Angelo M Zheng Qizhi Carvalho Benilton Morgan James D He Tony L Badrinath Raghav Aryee Martin J Esopi David Haffner Michael C Wu Zhijin Yegnasubramanian Srinivasan Irizarry Rafael A Nelson William G |
| author_facet | De Marzo Angelo M Zheng Qizhi Carvalho Benilton Morgan James D He Tony L Badrinath Raghav Aryee Martin J Esopi David Haffner Michael C Wu Zhijin Yegnasubramanian Srinivasan Irizarry Rafael A Nelson William G |
| author_sort | De Marzo Angelo M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>DNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD) followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells.</p> <p>Results</p> <p>Examining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (<it>ADAMTS1 </it>and <it>SCARF2 </it>genes) and non-promoter (downstream or within <it>DSCR9</it>, <it>C21orf57 </it>and <it>HLCS </it>genes) hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines.</p> <p>Conclusions</p> <p>Comparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.</p> |
| first_indexed | 2024-12-11T13:14:09Z |
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| id | doaj.art-6cb7fca4f93d4531b84252623ee28800 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-11T13:14:09Z |
| publishDate | 2011-06-01 |
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| spelling | doaj.art-6cb7fca4f93d4531b84252623ee288002022-12-22T01:06:06ZengBMCBMC Genomics1471-21642011-06-0112131310.1186/1471-2164-12-313Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequencesDe Marzo Angelo MZheng QizhiCarvalho BeniltonMorgan James DHe Tony LBadrinath RaghavAryee Martin JEsopi DavidHaffner Michael CWu ZhijinYegnasubramanian SrinivasanIrizarry Rafael ANelson William G<p>Abstract</p> <p>Background</p> <p>DNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD) followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells.</p> <p>Results</p> <p>Examining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (<it>ADAMTS1 </it>and <it>SCARF2 </it>genes) and non-promoter (downstream or within <it>DSCR9</it>, <it>C21orf57 </it>and <it>HLCS </it>genes) hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines.</p> <p>Conclusions</p> <p>Comparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.</p>http://www.biomedcentral.com/1471-2164/12/313DNA methylationprostate cancertiling microarrayepigeneticsmethylated DNA binding domainMBD-chipADAMTS1SCARF2DSCR9HLCS |
| spellingShingle | De Marzo Angelo M Zheng Qizhi Carvalho Benilton Morgan James D He Tony L Badrinath Raghav Aryee Martin J Esopi David Haffner Michael C Wu Zhijin Yegnasubramanian Srinivasan Irizarry Rafael A Nelson William G Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences BMC Genomics DNA methylation prostate cancer tiling microarray epigenetics methylated DNA binding domain MBD-chip ADAMTS1 SCARF2 DSCR9 HLCS |
| title | Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences |
| title_full | Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences |
| title_fullStr | Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences |
| title_full_unstemmed | Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences |
| title_short | Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences |
| title_sort | chromosome wide mapping of dna methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene associated and conserved intergenic sequences |
| topic | DNA methylation prostate cancer tiling microarray epigenetics methylated DNA binding domain MBD-chip ADAMTS1 SCARF2 DSCR9 HLCS |
| url | http://www.biomedcentral.com/1471-2164/12/313 |
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