Journal
NATURE GENETICS
Volume 47, Issue 7, Pages 746-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3291
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Funding
- European Union's Seventh Framework Programme through the Blueprint Consortium [282510]
- Spanish Ministry of Economy and Competitivity (MINECO) [SAF2009-08663]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR
- Generalitat de Catalunya)
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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.
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