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Epigenetics Chromatin. 2016 Jul 29;9:33. doi: 10.1186/s13072-016-0079-z. eCollection 2016.

Epigenetic dynamics of monocyte-to-macrophage differentiation.

Author information

1
Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
2
Genome Informatics, Institute of Human Genetics, University Duisburg-Essen, Essen, Germany.
3
Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
4
Bioinformatics and Deep Sequencing Unit, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
5
Max Delbrück-Center for Molecular Medicine, Berlin, Germany.
6
Max Planck Institute for Informatics, Saarbrücken, Germany.
7
Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
8
Institute of Genetics/Epigenetics, Saarland University, Saarbrücken, Germany.
9
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
10
Biochip Lab, Institute of Cell Biology, University Duisburg-Essen, Essen, Germany.
11
Caritas Krankenhaus St. Josef, Regensburg, Germany.

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.

KEYWORDS:

DEEP; Enhancer; Epigenetics; IHEC; Macrophage; Methylation; Monocyte; Next-generation sequencing; TET; Ten eleven translocation methylcytosine dioxygenase

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