Blood Journal
Leading the way in experimental and clinical research in hematology

Transcription and enhancer profiling in human monocyte subsets

  1. Christian Schmidl1,
  2. Kathrin Renner1,
  3. Katrin Peter1,
  4. Ruediger Eder1,
  5. Timo Lassmann2,
  6. Piotr J. Balwierz3,
  7. Masayoshi Itoh4,
  8. Sayaka Nagao-Sato2,
  9. Hideya Kawaji5,
  10. Piero Carninci2,
  11. Harukazu Suzuki2,
  12. Yoshihide Hayashizaki2,
  13. Reinhard Andreesen6,
  14. David A. Hume7,
  15. Petra Hoffmann1,
  16. Alistair R. R. Forrest2,
  17. Marina P. Kreutz1,
  18. Matthias Edinger1, and
  19. Michael Rehli1,*
  1. 1 Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany;
  2. 2 RIKEN Omics Science Center, Yokohama Institute, Kanagawa, Japan;
  3. 3 Biozentrum, University of Basel, Basel, Switzerland;
  4. 4 RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan;
  5. 5 RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan;
  6. 6 Regensburg Centre for Interventional Immunology (RCI), Regensburg, Germany;
  7. 7 The Roslin Institute and Royal (Dick) School of Veterinary Studies, Edinburgh University, Midlothian, Scotland, United Kingdom
  1. * Corresponding author; email: michael.rehli{at}

Key points

  • In-depth regulome analysis of human monocyte subsets, including transcription and enhancer profiling.

  • Description of metabolomic differences in human monocyte subsets.


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 (CD14dimCD16+) 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.

  • Submitted February 11, 2013.
  • Accepted May 7, 2013.