Epigenetic dynamics of monocyte-to-macrophage differentiation.

Authors:
Stefan Wallner, Christopher Schröder, Elsa Leitão, Tea Berulava, Claudia Haak, Daniela Beißer, Sven Rahmann, Andreas S Richter, Thomas Manke, Ulrike Bönisch, Laura Arrigoni, Sebastian Fröhler, Filippos Klironomos, Wei Chen, Nikolaus Rajewsky, Fabian Müller, Peter Ebert, Thomas Lengauer, Matthias Barann, Philip Rosenstiel, Gilles Gasparoni, Karl Nordström, Jörn Walter, Benedikt Brors, Gideon Zipprich, Bärbel Felder, Ludger Klein-Hitpass, Corinna Attenberger, Gerd Schmitz, Bernhard Horsthemke
Year of publication:
2016
Volume:
9
Issue:
-
Issn:
1756-8935
Journal title abbreviated:
EPIGENET CHROMATIN
Journal title long:
Epigenetics & chromatin
Impact factor:
5.189
Abstract:
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.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.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.