title: Characterization of the DNA methylome and its interindividual variation in human peripheral blood monocytes.
abstract: OBJECTIVE
  Peripheral blood monocytes (PBMs) play multiple and critical roles in the immune response, and abnormalities in PBMs have been linked to a variety of human disorders. However, the DNA methylation landscape in PBMs is largely unknown. In this study, we characterized epigenome-wide DNA methylation profiles in purified PBMs.
  
  
  METHODS
  PBMs were isolated from freshly collected peripheral blood from 18 unrelated healthy postmenopausal Caucasian females. Epigenome-wide DNA methylation profiles (the methylome) were characterized by using methylated DNA immunoprecipitation combined with high-throughput sequencing.
  
  
  RESULTS
  Distinct patterns were revealed at different genomic features. For instance, promoters were commonly (∼58%) found to be unmethylated; whereas protein coding regions were largely (∼84%) methylated. Although CpG-rich and -poor promoters showed distinct methylation patterns, interestingly, a negative correlation between promoter methylation levels and gene transcription levels was consistently observed across promoters with high to low CpG densities. Importantly, we observed substantial interindividual variation in DNA methylation across the individual PBM methylomes and the pattern of this interindividual variation varied between different genomic features, with highly variable regions enriched for repetitive DNA elements. Furthermore, we observed a modest but significant excess (p < 2.2 × 10(-16)) of genes showing a negative correlation between interindividual promoter methylation and transcription levels. These significant genes were enriched in biological processes that are closely related to PBM functions, suggesting that alteration in DNA methylation is likely to be an important mechanism contributing to the interindividual variation in PBM function, and PBM-related phenotypic and disease-susceptibility variation in humans.
  
  
  CONCLUSIONS
  This study represents a comprehensive analysis of the human PBM methylome and its interindividual variation. Our data provide a valuable resource for future epigenomic and multiomic studies, exploring biological and disease-related regulatory mechanisms in PBMs.
authors.affiliation: Center for Bioinformatics & Genomics, Department of Biostatistics & Bioinformatics, School of Public Health & Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Chuan
authors.initials: C
authors.lastname: Qiu
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic