Genome-Wide DNA Methylation Maps in Follicular Lymphoma Cells Determined by Methylation-Enriched Bisulfite Sequencing

Hdl Handle:
http://hdl.handle.net/10675.2/599
Title:
Genome-Wide DNA Methylation Maps in Follicular Lymphoma Cells Determined by Methylation-Enriched Bisulfite Sequencing
Authors:
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
Abstract:
Background: 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.; Methodology/Principal Findings: 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.; Conclusions/Significance: 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.
Citation:
PLoS One. 2010 Sep 29; 5(9):e13020
Issue Date:
29-Sep-2010
URI:
http://hdl.handle.net/10675.2/599
DOI:
10.1371/journal.pone.0013020
PubMed ID:
20927367
PubMed Central ID:
PMC2947499
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Georgia Cancer Center: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorChoi, Jeong-Hyeonen_US
dc.contributor.authorLi, Yajunen_US
dc.contributor.authorGuo, Juyuanen_US
dc.contributor.authorPei, Lirongen_US
dc.contributor.authorRauch, Tibor A.en_US
dc.contributor.authorKramer, Robin S.en_US
dc.contributor.authorMacmil, Simone L.en_US
dc.contributor.authorWiley, Graham B.en_US
dc.contributor.authorBennett, Lynda B.en_US
dc.contributor.authorSchnabel, Jennifer L.en_US
dc.contributor.authorTaylor, Kristen H.en_US
dc.contributor.authorKim, Sunen_US
dc.contributor.authorXu, Dongen_US
dc.contributor.authorSreekumar, Arunen_US
dc.contributor.authorPfeifer, Gerd P.en_US
dc.contributor.authorRoe, Bruce A.en_US
dc.contributor.authorCaldwell, Charles W.en_US
dc.contributor.authorBhalla, Kapil N.en_US
dc.contributor.authorShi, Huidongen_US
dc.date.accessioned2012-10-26T16:26:50Z-
dc.date.available2012-10-26T16:26:50Z-
dc.date.issued2010-09-29en_US
dc.identifier.citationPLoS One. 2010 Sep 29; 5(9):e13020en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid20927367en_US
dc.identifier.doi10.1371/journal.pone.0013020en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/599-
dc.description.abstractBackground: 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.en_US
dc.description.abstractMethodology/Principal Findings: 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.en_US
dc.description.abstractConclusions/Significance: 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.en_US
dc.rightsChoi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectGenetics and Genomics/Epigeneticsen_US
dc.subjectGenetics and Genomics/Gene Expressionen_US
dc.subjectOncology/Hematological Malignanciesen_US
dc.subject.meshB-Lymphocytesen_US
dc.subject.meshDNA Methylationen_US
dc.subject.meshGenome, Humanen_US
dc.subject.meshGenome-Wide Association Studyen_US
dc.subject.meshHumansen_US
dc.subject.meshLymphoma, Follicularen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshSequence Analysis, DNAen_US
dc.subject.meshSulfitesen_US
dc.titleGenome-Wide DNA Methylation Maps in Follicular Lymphoma Cells Determined by Methylation-Enriched Bisulfite Sequencingen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2947499en_US
dc.contributor.corporatenameGHSU Cancer Center-

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