title: Genome-wide methylation analyses of primary human leukocyte subsets identifies functionally important cell-type-specific hypomethylated regions.
abstract: 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.
authors.affiliation: Department of Medicine and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Zilbauer
authors.forename: Tim F
authors.initials: TF
authors.lastname: Rayner
authors.forename: Christine
authors.initials: C
authors.lastname: Clark
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Coffey
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Joyce
authors.forename: Priit
authors.initials: P
authors.lastname: Palta
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019175:DNA Methylation / Q000235:genetics / Q000276:immunology*; D015894:Genome, Human / Q000235:genetics / Q000276:immunology*; D055106:Genome-Wide Association Study; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology*