title: Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells.
abstract: The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream ofIRF8and an intronic enhancer in theKITgene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity.
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan anagha.joshi@roslin.ed.ac.uk david.hume@roslin.ed.ac.uk.
authors.forename: Anagha
authors.initials: A
authors.lastname: Joshi
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pooley
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Tom C
authors.initials: TC
authors.lastname: Freeman
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lennartsson
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Magda
authors.initials: M
authors.lastname: Babina
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidl
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Teunis
authors.initials: T
authors.lastname: Geijtenbeek
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Tom
authors.initials: T
authors.lastname: Michoel
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Jessica
authors.initials: J
authors.lastname: Severin
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Itoh
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan.
authors.forename: Michael
authors.initials: M
authors.lastname: Rehli
authors.affiliation: *The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, United Kingdom; RIKEN Preventive Medicine and Diagnosis Innovation Program, Tsurumi-ku, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Tsurumi-ku, Yokohama, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden; Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany; Department of Internal Medicine III, University Hospital, University of Regensburg, Germany; Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands; and **RIKEN Omics Science Center, Tsurumi-ku, Yokohama, Japan anagha.joshi@roslin.ed.ac.uk david.hume@roslin.ed.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
keywords: CAGE; hematopoiesis; transcriptome