Genome-wide DNA methylation maps in follicular lymphoma cells determined by methylation-enriched bisulfite sequencing
Follicular lymphoma (FL) is a form of non-Hodgkin's lymphoma (NHL) that arises from germinal center (GC) B-cells. Despite the significant advances in immunotherapy, FL is still not curable. Beyond transcriptional profiling and genomics datasets, there currently is no epigenome-scale dataset or...
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| Veröffentlicht in: | PloS one 2010-09, Vol.5 (9), p.e13020 |
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| creator | Choi, Jeong-Hyeon Li, Yajun Guo, Juyuan Pei, Lirong Rauch, Tibor A Kramer, Robin S Macmil, Simone L Wiley, Graham B Bennett, Lynda B Schnabel, Jennifer L Taylor, Kristen H Kim, Sun Xu, Dong Sreekumar, Arun Pfeifer, Gerd P Roe, Bruce A Caldwell, Charles W Bhalla, Kapil N Shi, Huidong |
| description | Follicular lymphoma (FL) is a form of non-Hodgkin's lymphoma (NHL) that arises from germinal center (GC) B-cells. Despite the significant advances in immunotherapy, FL is still not curable. Beyond transcriptional profiling and genomics datasets, there currently is no epigenome-scale dataset or integrative biology approach that can adequately model this disease and therefore identify novel mechanisms and targets for successful prevention and treatment of FL.
We performed methylation-enriched genome-wide bisulfite sequencing of FL cells and normal CD19(+) B-cells using 454 sequencing technology. The methylated DNA fragments were enriched with methyl-binding proteins, treated with bisulfite, and sequenced using the Roche-454 GS FLX sequencer. The total number of bases covered in the human genome was 18.2 and 49.3 million including 726,003 and 1.3 million CpGs in FL and CD19(+) B-cells, respectively. 11,971 and 7,882 methylated regions of interest (MRIs) were identified respectively. The genome-wide distribution of these MRIs displayed significant differences between FL and normal B-cells. A reverse trend in the distribution of MRIs between the promoter and the gene body was observed in FL and CD19(+) B-cells. The MRIs identified in FL cells also correlated well with transcriptomic data and ChIP-on-Chip analyses of genome-wide histone modifications such as tri-methyl-H3K27, and tri-methyl-H3K4, indicating a concerted epigenetic alteration in FL cells.
This study is the first to provide a large scale and comprehensive analysis of the DNA methylation sequence composition and distribution in the FL epigenome. These integrated approaches have led to the discovery of novel and frequent targets of aberrant epigenetic alterations. The genome-wide bisulfite sequencing approach developed here can be a useful tool for profiling DNA methylation in clinical samples. |
| doi_str_mv | 10.1371/journal.pone.0013020 |
| format | Article |
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We performed methylation-enriched genome-wide bisulfite sequencing of FL cells and normal CD19(+) B-cells using 454 sequencing technology. The methylated DNA fragments were enriched with methyl-binding proteins, treated with bisulfite, and sequenced using the Roche-454 GS FLX sequencer. The total number of bases covered in the human genome was 18.2 and 49.3 million including 726,003 and 1.3 million CpGs in FL and CD19(+) B-cells, respectively. 11,971 and 7,882 methylated regions of interest (MRIs) were identified respectively. The genome-wide distribution of these MRIs displayed significant differences between FL and normal B-cells. A reverse trend in the distribution of MRIs between the promoter and the gene body was observed in FL and CD19(+) B-cells. The MRIs identified in FL cells also correlated well with transcriptomic data and ChIP-on-Chip analyses of genome-wide histone modifications such as tri-methyl-H3K27, and tri-methyl-H3K4, indicating a concerted epigenetic alteration in FL cells.
This study is the first to provide a large scale and comprehensive analysis of the DNA methylation sequence composition and distribution in the FL epigenome. These integrated approaches have led to the discovery of novel and frequent targets of aberrant epigenetic alterations. The genome-wide bisulfite sequencing approach developed here can be a useful tool for profiling DNA methylation in clinical samples.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0013020</identifier><identifier>PMID: 20927367</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Analysis ; B cells ; B-Lymphocytes - metabolism ; Binding proteins ; Bioinformatics ; Bisulfite ; Cancer ; Care and treatment ; CD19 antigen ; Data processing ; Deoxyribonucleic acid ; DNA ; DNA fingerprinting ; DNA Methylation ; DNA sequencing ; Enrichment ; Epigenetic inheritance ; Epigenetics ; Gene expression ; Gene mapping ; Gene sequencing ; Genes ; Genetic aspects ; Genetics and Genomics/Epigenetics ; Genetics and Genomics/Gene Expression ; Genome, Human ; Genome-Wide Association Study ; Genomes ; Genomics ; Hematology ; Humans ; Immunotherapy ; Lung cancer ; Lymphocytes B ; Lymphoma ; Lymphoma, Follicular - genetics ; Lymphoma, Follicular - metabolism ; Medical research ; Methylation ; Non-Hodgkin's lymphoma ; Non-Hodgkin's lymphomas ; Nucleotide sequence ; Oncology/Hematological Malignancies ; Pathology ; Promoter Regions, Genetic ; Prostate cancer ; Protein binding ; Protein expression ; Proteins ; Sequence Analysis, DNA - methods ; Sulfites ; Sulfites - chemistry ; Target recognition ; Transcription ; Tumors</subject><ispartof>PloS one, 2010-09, Vol.5 (9), p.e13020</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Choi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Choi et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-6158b5c822d18c388ab6875cb648266b747ccd7199672da182f57766bf4756033</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947499/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947499/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20927367$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tan, Patrick</contributor><creatorcontrib>Choi, Jeong-Hyeon</creatorcontrib><creatorcontrib>Li, Yajun</creatorcontrib><creatorcontrib>Guo, Juyuan</creatorcontrib><creatorcontrib>Pei, Lirong</creatorcontrib><creatorcontrib>Rauch, Tibor A</creatorcontrib><creatorcontrib>Kramer, Robin S</creatorcontrib><creatorcontrib>Macmil, Simone L</creatorcontrib><creatorcontrib>Wiley, Graham B</creatorcontrib><creatorcontrib>Bennett, Lynda B</creatorcontrib><creatorcontrib>Schnabel, Jennifer L</creatorcontrib><creatorcontrib>Taylor, Kristen H</creatorcontrib><creatorcontrib>Kim, Sun</creatorcontrib><creatorcontrib>Xu, Dong</creatorcontrib><creatorcontrib>Sreekumar, Arun</creatorcontrib><creatorcontrib>Pfeifer, Gerd P</creatorcontrib><creatorcontrib>Roe, Bruce A</creatorcontrib><creatorcontrib>Caldwell, Charles W</creatorcontrib><creatorcontrib>Bhalla, Kapil N</creatorcontrib><creatorcontrib>Shi, Huidong</creatorcontrib><title>Genome-wide DNA methylation maps in follicular lymphoma cells determined by methylation-enriched bisulfite sequencing</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Follicular lymphoma (FL) is a form of non-Hodgkin's lymphoma (NHL) that arises from germinal center (GC) B-cells. Despite the significant advances in immunotherapy, FL is still not curable. Beyond transcriptional profiling and genomics datasets, there currently is no epigenome-scale dataset or integrative biology approach that can adequately model this disease and therefore identify novel mechanisms and targets for successful prevention and treatment of FL.
We performed methylation-enriched genome-wide bisulfite sequencing of FL cells and normal CD19(+) B-cells using 454 sequencing technology. The methylated DNA fragments were enriched with methyl-binding proteins, treated with bisulfite, and sequenced using the Roche-454 GS FLX sequencer. The total number of bases covered in the human genome was 18.2 and 49.3 million including 726,003 and 1.3 million CpGs in FL and CD19(+) B-cells, respectively. 11,971 and 7,882 methylated regions of interest (MRIs) were identified respectively. The genome-wide distribution of these MRIs displayed significant differences between FL and normal B-cells. A reverse trend in the distribution of MRIs between the promoter and the gene body was observed in FL and CD19(+) B-cells. The MRIs identified in FL cells also correlated well with transcriptomic data and ChIP-on-Chip analyses of genome-wide histone modifications such as tri-methyl-H3K27, and tri-methyl-H3K4, indicating a concerted epigenetic alteration in FL cells.
This study is the first to provide a large scale and comprehensive analysis of the DNA methylation sequence composition and distribution in the FL epigenome. These integrated approaches have led to the discovery of novel and frequent targets of aberrant epigenetic alterations. The genome-wide bisulfite sequencing approach developed here can be a useful tool for profiling DNA methylation in clinical samples.</description><subject>Aberration</subject><subject>Analysis</subject><subject>B cells</subject><subject>B-Lymphocytes - metabolism</subject><subject>Binding proteins</subject><subject>Bioinformatics</subject><subject>Bisulfite</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>CD19 antigen</subject><subject>Data processing</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA fingerprinting</subject><subject>DNA Methylation</subject><subject>DNA sequencing</subject><subject>Enrichment</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>Gene mapping</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetics and Genomics/Epigenetics</subject><subject>Genetics and Genomics/Gene Expression</subject><subject>Genome, Human</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Lung cancer</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Lymphoma, Follicular - genetics</subject><subject>Lymphoma, Follicular - metabolism</subject><subject>Medical research</subject><subject>Methylation</subject><subject>Non-Hodgkin's lymphoma</subject><subject>Non-Hodgkin's lymphomas</subject><subject>Nucleotide sequence</subject><subject>Oncology/Hematological Malignancies</subject><subject>Pathology</subject><subject>Promoter Regions, Genetic</subject><subject>Prostate cancer</subject><subject>Protein binding</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Sulfites</subject><subject>Sulfites - 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Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Jeong-Hyeon</au><au>Li, Yajun</au><au>Guo, Juyuan</au><au>Pei, Lirong</au><au>Rauch, Tibor A</au><au>Kramer, Robin S</au><au>Macmil, Simone L</au><au>Wiley, Graham B</au><au>Bennett, Lynda B</au><au>Schnabel, Jennifer L</au><au>Taylor, Kristen H</au><au>Kim, Sun</au><au>Xu, Dong</au><au>Sreekumar, Arun</au><au>Pfeifer, Gerd P</au><au>Roe, Bruce A</au><au>Caldwell, Charles W</au><au>Bhalla, Kapil N</au><au>Shi, Huidong</au><au>Tan, Patrick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide DNA methylation maps in follicular lymphoma cells determined by methylation-enriched bisulfite sequencing</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-09-29</date><risdate>2010</risdate><volume>5</volume><issue>9</issue><spage>e13020</spage><pages>e13020-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Follicular lymphoma (FL) is a form of non-Hodgkin's lymphoma (NHL) that arises from germinal center (GC) B-cells. Despite the significant advances in immunotherapy, FL is still not curable. Beyond transcriptional profiling and genomics datasets, there currently is no epigenome-scale dataset or integrative biology approach that can adequately model this disease and therefore identify novel mechanisms and targets for successful prevention and treatment of FL.
We performed methylation-enriched genome-wide bisulfite sequencing of FL cells and normal CD19(+) B-cells using 454 sequencing technology. The methylated DNA fragments were enriched with methyl-binding proteins, treated with bisulfite, and sequenced using the Roche-454 GS FLX sequencer. The total number of bases covered in the human genome was 18.2 and 49.3 million including 726,003 and 1.3 million CpGs in FL and CD19(+) B-cells, respectively. 11,971 and 7,882 methylated regions of interest (MRIs) were identified respectively. The genome-wide distribution of these MRIs displayed significant differences between FL and normal B-cells. A reverse trend in the distribution of MRIs between the promoter and the gene body was observed in FL and CD19(+) B-cells. The MRIs identified in FL cells also correlated well with transcriptomic data and ChIP-on-Chip analyses of genome-wide histone modifications such as tri-methyl-H3K27, and tri-methyl-H3K4, indicating a concerted epigenetic alteration in FL cells.
This study is the first to provide a large scale and comprehensive analysis of the DNA methylation sequence composition and distribution in the FL epigenome. These integrated approaches have led to the discovery of novel and frequent targets of aberrant epigenetic alterations. The genome-wide bisulfite sequencing approach developed here can be a useful tool for profiling DNA methylation in clinical samples.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20927367</pmid><doi>10.1371/journal.pone.0013020</doi><tpages>e13020</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2010-09, Vol.5 (9), p.e13020 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1292344808 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aberration Analysis B cells B-Lymphocytes - metabolism Binding proteins Bioinformatics Bisulfite Cancer Care and treatment CD19 antigen Data processing Deoxyribonucleic acid DNA DNA fingerprinting DNA Methylation DNA sequencing Enrichment Epigenetic inheritance Epigenetics Gene expression Gene mapping Gene sequencing Genes Genetic aspects Genetics and Genomics/Epigenetics Genetics and Genomics/Gene Expression Genome, Human Genome-Wide Association Study Genomes Genomics Hematology Humans Immunotherapy Lung cancer Lymphocytes B Lymphoma Lymphoma, Follicular - genetics Lymphoma, Follicular - metabolism Medical research Methylation Non-Hodgkin's lymphoma Non-Hodgkin's lymphomas Nucleotide sequence Oncology/Hematological Malignancies Pathology Promoter Regions, Genetic Prostate cancer Protein binding Protein expression Proteins Sequence Analysis, DNA - methods Sulfites Sulfites - chemistry Target recognition Transcription Tumors |
| title | Genome-wide DNA methylation maps in follicular lymphoma cells determined by methylation-enriched bisulfite sequencing |
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