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Whole-genome fingerprint of the DNA methylome during human B cell differentiation

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. Green open access

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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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