title: Epigenetic dynamics of monocyte-to-macrophage differentiation.
abstract: BACKGROUND
  Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium.
  
  
  RESULTS
  Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response.
  
  
  CONCLUSIONS
  In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation.
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wallner
authors.affiliation: Genome Informatics, Institute of Human Genetics, University Duisburg-Essen, Essen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Schröder
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
authors.forename: Elsa
authors.initials: E
authors.lastname: Leitão
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
authors.forename: Tea
authors.initials: T
authors.lastname: Berulava
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Haak
authors.affiliation: Genome Informatics, Institute of Human Genetics, University Duisburg-Essen, Essen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Beißer
authors.affiliation: Genome Informatics, Institute of Human Genetics, University Duisburg-Essen, Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Rahmann
authors.affiliation: Bioinformatics and Deep Sequencing Unit, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Richter
authors.affiliation: Bioinformatics and Deep Sequencing Unit, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Manke
authors.affiliation: Bioinformatics and Deep Sequencing Unit, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bönisch
authors.affiliation: Bioinformatics and Deep Sequencing Unit, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Arrigoni
authors.affiliation: Max Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fröhler
authors.affiliation: Max Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Filippos
authors.initials: F
authors.lastname: Klironomos
authors.affiliation: Max Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Max Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Rajewsky
authors.affiliation: Max Planck Institute for Informatics, Saarbrücken, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Müller
authors.affiliation: Max Planck Institute for Informatics, Saarbrücken, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ebert
authors.affiliation: Max Planck Institute for Informatics, Saarbrücken, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lengauer
authors.affiliation: Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Barann
authors.affiliation: Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.affiliation: Institute of Genetics/Epigenetics, Saarland University, Saarbrücken, Germany.
authors.forename: Gilles
authors.initials: G
authors.lastname: Gasparoni
authors.affiliation: Institute of Genetics/Epigenetics, Saarland University, Saarbrücken, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Nordström
authors.affiliation: Institute of Genetics/Epigenetics, Saarland University, Saarbrücken, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Walter
authors.affiliation: Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.affiliation: Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Gideon
authors.initials: G
authors.lastname: Zipprich
authors.affiliation: Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Felder
authors.affiliation: Biochip Lab, Institute of Cell Biology, University Duisburg-Essen, Essen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.affiliation: Caritas Krankenhaus St. Josef, Regensburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Attenberger
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.affiliation: Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
keywords: DEEP; Enhancer; Epigenetics; IHEC; Macrophage; Methylation; Monocyte; Next-generation sequencing; TET; Ten eleven translocation methylcytosine dioxygenase