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Genome-wide methylation analyses of primary human leukocyte subsets identifies functionally important cell-type–specific hypomethylated regions

2013; Elsevier BV; Volume: 122; Issue: 25 Linguagem: Inglês

10.1182/blood-2013-05-503201

1528-0020

Matthias Zilbauer, Tim F. Rayner, Christine Clark, Alison J. Coffey, Chris J. Joyce, Priit Palta, Aarno Palotie, Paul Lyons, Kenneth G. C. Smith,

RNA modifications and cancer

DNA methylation is an important mechanism by which gene transcription and hence cellular function are regulated. Here, we provide detailed functional genome-wide methylome maps of 5 primary peripheral blood leukocyte subsets including T cells, B cells, monocytes/macrophages, and neutrophils obtained from healthy individuals. A comparison of these methylomes revealed highly specific cell-lineage and cell-subset methylation profiles. DNA hypomethylation is known to be permissive for gene expression and we identified cell-subset-specific hypomethylated regions (HMRs) that strongly correlate with gene transcription levels suggesting these HMRs may regulate corresponding cell functions. Single-nucleotide polymorphisms associated with immune-mediated disease in genome-wide association studies preferentially localized to these cell-specific regulatory HMRs, offering insight into pathogenesis by highlighting cell subsets in which specific epigenetic changes may drive disease. Our data provide a valuable reference tool for researchers aiming to investigate the role of DNA methylation in regulating primary leukocyte function in health and immune-mediated disease.