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Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals

Glossop, John R.; Nixon, Nicola B.; Emes, Richard D.; Haworth, Kim E.; Packham, Jon C.; Dawes, Peter T.; Fryer, Anthony A.; Mattey, Derek L.; Farrell, William E.

Authors

John R. Glossop

Nicola B. Nixon

Richard D. Emes

Kim E. Haworth

Jon C. Packham

Peter T. Dawes

Anthony A. Fryer

Derek L. Mattey

William E. Farrell



Abstract

Multiple reports now describe changes to the DNA methylome in rheumatoid arthritis and in many cases have analyzed methylation in mixed cell populations from whole blood. However, these approaches may preclude the identification of cell type-specific methylation, which may subsequently bias identification of disease-specific changes. To address this possibility, we conducted genome-wide DNA methylation profiling using HumanMethylation450 BeadChips to identify differences within matched pairs of T-lymphocytes and B-lymphocytes isolated from the peripheral blood of 10 healthy females. Array data were processed and differential methylation identified using NIMBL software. Validation of array data was performed by bisulfite Pyrosequencing. Genome-wide DNA methylation was initially determined by analysis of LINE-1 sequences and was higher in B-lymphocytes than matched T-lymphocytes (69.8 vs. 65.2%, p ≤ 0.01). Pairwise analysis identified 679 CpGs, representing 250 genes, which were differentially methylated between T-lymphocytes and B-lymphocytes. The majority of sites (76.6%) were hypermethylated in B-lymphocytes. Pyrosequencing of selected candidates confirmed the array data in all cases. Hierarchical clustering revealed perfect segregation of samples into two distinct clusters based on cell type. Differentially methylated genes showed enrichment for biological functions/pathways associated with leukocytes and T-lymphocytes. Our work for the first time shows that T-lymphocytes and B-lymphocytes possess intrinsic differences in DNA methylation within a restricted set of functionally-related genes. These data provide a foundation for investigating DNA methylation in diseases in which these cell types play important and distinct roles.

Journal Article Type Article
Publication Date Jan 1, 2013
Journal Epigenetics
Print ISSN 1559-2294
Electronic ISSN 1559-2294
Publisher Taylor & Francis
Peer Reviewed Peer Reviewed
Volume 8
Issue 11
APA6 Citation Glossop, J. R., Nixon, N. B., Emes, R. D., Haworth, K. E., Packham, J. C., Dawes, P. T., …Farrell, W. E. (2013). Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals. Epigenetics, 8(11), doi:10.4161/epi.26265
DOI https://doi.org/10.4161/epi.26265
Publisher URL http://www.tandfonline.com/doi/abs/10.4161/epi.26265
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Glossop et al. Epigenetics 2013.8.1188-97.pdf (345 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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