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

• Published in: Blood 2013-12, Vol.122 (25), p.e52-e60
• Main Authors: Zilbauer, Matthias, Rayner, Tim F., Clark, Christine, Coffey, Alison J., Joyce, Chris J., Palta, Priit, Palotie, Aarno, Lyons, Paul A., Smith, Kenneth G.C.
• Format: Article
• Language: English
• Subjects: Adult; B-Lymphocyte Subsets - immunology; DNA Methylation - genetics; DNA Methylation - immunology; Genome, Human - genetics; Genome, Human - immunology; Genome-Wide Association Study; Humans; Immune System Diseases - genetics; Immune System Diseases - immunology; Immune System Diseases - pathology; Male; Middle Aged; Phagocytes, Granulocytes, and Myelopoiesis; Polymorphism, Single Nucleotide; T-Lymphocyte Subsets - immunology; Transcription, Genetic - genetics; Transcription, Genetic - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-05-503201

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. •We provide a functional DNA methylation map of human leukocyte subsets and identify cell-type–specific regulatory HMRs.•We illustrate use of this data by demonstrating a potential link between gene polymorphisms, DNA methylation, and immune-mediated disease.