Schmidl, Christian and Renner, Kathrin and Peter, Katrin and Eder, Ruediger and Lassmann, Timo and Balwierz, Piotr J. and Itoh, Masayoshi and Nagao-Sato, Sayaka and Kawaji, Hideya and Carninci, Piero and Suzuki, Harukazu and Hayashizaki, Yoshihide and Andreesen, Reinhard and Hume, David A. and Hoffmann, Petra and Forrest, Alistair R. R. and Kreutz, Marina P. and Edinger, Matthias and Rehli, Michael (2014) Transcription and enhancer profiling in human monocyte subsets. BLOOD, 123 (17). E90-E99. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-EXPRESSION; DIFFERENTIATION; HETEROGENEITY; MACROPHAGE; SIGNATURES; DISTINCT; REVEALS; APOPTOSIS; PROTEINS; CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Nov 2019 15:14 |
| Last Modified: | 13 Nov 2019 15:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10292 |
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