Kulis, M;
Merkel, A;
Heath, S;
Queirós, AC;
Schuyler, RP;
Castellano, G;
Beekman, R;
... Martín-Subero, JI; + view all
(2015)
Whole-genome fingerprint of the DNA methylome during human B cell differentiation.
Nature Genetics
, 47
(7)
pp. 746-756.
10.1038/ng.3291.
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Abstract
We analyzed the DNA methylome of ten subpopulations spanning the entire B cell differentiation program by whole-genome bisulfite sequencing and high-density microarrays. We observed that non-CpG methylation disappeared upon B cell commitment, whereas CpG methylation changed extensively during B cell maturation, showing an accumulative pattern and affecting around 30% of all measured CpG sites. Early differentiation stages mainly displayed enhancer demethylation, which was associated with upregulation of key B cell transcription factors and affected multiple genes involved in B cell biology. Late differentiation stages, in contrast, showed extensive demethylation of heterochromatin and methylation gain at Polycomb-repressed areas, and genes with apparent functional impact in B cells were not affected. This signature, which has previously been linked to aging and cancer, was particularly widespread in mature cells with an extended lifespan. Comparing B cell neoplasms with their normal counterparts, we determined that they frequently acquire methylation changes in regions already undergoing dynamic methylation during normal B cell differentiation.
| Type: | Article |
|---|---|
| Title: | Whole-genome fingerprint of the DNA methylome during human B cell differentiation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ng.3291 |
| Publisher version: | http://dx.doi.org/10.1038/ng.3291 |
| Language: | English |
| Additional information: | © 2015 Nature America, Inc. All rights reserved. |
| Keywords: | Epigenomics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1530101 |
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