John R. Glossop
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
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.
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), https://doi.org/10.4161/epi.26265
Journal Article Type | Article |
---|---|
Publication Date | Jan 1, 2013 |
Deposit Date | Dec 18, 2015 |
Publicly Available Date | Dec 18, 2015 |
Journal | Epigenetics |
Print ISSN | 1559-2294 |
Electronic ISSN | 1559-2308 |
Publisher | Taylor and Francis |
Peer Reviewed | Peer Reviewed |
Volume | 8 |
Issue | 11 |
DOI | https://doi.org/10.4161/epi.26265 |
Public URL | https://nottingham-repository.worktribe.com/output/1004237 |
Publisher URL | http://www.tandfonline.com/doi/abs/10.4161/epi.26265 |
Files
Glossop et al. Epigenetics 2013.8.1188-97.pdf
(345 Kb)
PDF
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search