Journal
BLOOD
Volume 123, Issue 17, Pages E90-E99Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-02-484188
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Funding
- MEXT
- MEXT, Japan
- Deutsche Forschungsgemeinschaft [DFG Re1310/9, Re1310/13]
- BayImmuNet
- Jose Carreras Foundation (FACS-Sorting Facility)
- Rudolf Bartling Foundation
- Biotechnology and Biological Sciences Research Council [BBS/E/D/20251969, BB/I024801/1] Funding Source: researchfish
- BBSRC [BB/I024801/1, BBS/E/D/20251969] Funding Source: UKRI
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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.
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