Christopher Schröder, Daniela Beißer and Sven Rahmann from the Genome Informatics group contributed to novel insights about epigenetic changes during cell differentiation. The article will appear soon in the renowned “Epigenetics & Chromatin” journal (IF 4.873) by BioMedCentral.
Epigenetic dynamics of monocyte to macrophage differentiation
by Stefan Wallner, Christopher Schröder, Elsa Leitão, Tea Berulava, Claudia
Haak, Daniela Beißer, Sven Rahmann, Andreas S Richter, Thomas Manke,
Ulrike Böhnisch, 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
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
(CSF1) in serum-free medium. Numerous mRNAs and miRNAs were
significantly up- or downregulated. More than 100 discrete DNA regions,
most often far away from transcription start sites, were rapidly
demethylated by the ten-eleven translocation (TET) 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.