title: Transcription and enhancer profiling in human monocyte subsets.
abstract: Human blood monocytes comprise at least 3 subpopulations that differ in phenotype and function. Here, we present the first in-depth regulome analysis of human classical (CD14(++)CD16(-)), intermediate (CD14(+)CD16(+)), and nonclassical (CD14(dim)CD16(+)) monocytes. Cap analysis of gene expression adapted to Helicos single-molecule sequencing was used to map transcription start sites throughout the genome in all 3 subsets. In addition, global maps of H3K4me1 and H3K27ac deposition were generated for classical and nonclassical monocytes defining enhanceosomes of the 2 major subsets. We identified differential regulatory elements (including promoters and putative enhancers) that were associated with subset-specific motif signatures corresponding to different transcription factor activities and exemplarily validated novel downstream enhancer elements at the CD14 locus. In addition to known subset-specific features, pathway analysis revealed marked differences in metabolic gene signatures. Whereas classical monocytes expressed higher levels of genes involved in carbohydrate metabolism, priming them for anaerobic energy production, nonclassical monocytes expressed higher levels of oxidative pathway components and showed a higher mitochondrial routine activity. Our findings describe promoter/enhancer landscapes and provide novel insights into the specific biology of human monocyte subsets.
authors.affiliation: Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidl
authors.forename: Kathrin
authors.initials: K
authors.lastname: Renner
authors.forename: Katrin
authors.initials: K
authors.lastname: Peter
authors.forename: Ruediger
authors.initials: R
authors.lastname: Eder
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Balwierz
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Itoh
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nagao-Sato
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Harukazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
authors.forename: Petra
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.forename: Marina P
authors.initials: MP
authors.lastname: Kreutz
authors.forename: Matthias
authors.initials: M
authors.lastname: Edinger
authors.forename: Michael
authors.initials: M
authors.lastname: Rehli
mesh_terms: D020816:Amino Acid Motifs; D050260:Carbohydrate Metabolism; D002469:Cell Separation; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D017452:Receptors, IgG / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D002950:Citrate (si)-Synthase