Whole-genome fingerprint of the DNA methylome during human B cell differentiation.
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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Related Subject Headings
- Sequence Analysis, DNA
- Leukemia, B-Cell
- Humans
- Genome, Human
- Gene Expression Regulation, Leukemic
- Epigenesis, Genetic
- Developmental Biology
- DNA Methylation
- CpG Islands
- Cells, Cultured
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sequence Analysis, DNA
- Leukemia, B-Cell
- Humans
- Genome, Human
- Gene Expression Regulation, Leukemic
- Epigenesis, Genetic
- Developmental Biology
- DNA Methylation
- CpG Islands
- Cells, Cultured