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Epigenetic dynamics of monocyte-to-macrophage differentiation

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 dif...

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Autores principales: Wallner, Stefan, Schröder, Christopher, Leitão, Elsa, Berulava, Tea, Haak, Claudia, Beißer, Daniela, Rahmann, Sven, Richter, Andreas S., Manke, Thomas, Bönisch, Ulrike, Arrigoni, Laura, Fröhler, Sebastian, Klironomos, Filippos, Chen, Wei, Rajewsky, Nikolaus, Müller, Fabian, Ebert, Peter, Lengauer, Thomas, Barann, Matthias, Rosenstiel, Philip, Gasparoni, Gilles, Nordström, Karl, Walter, Jörn, Brors, Benedikt, Zipprich, Gideon, Felder, Bärbel, Klein-Hitpass, Ludger, Attenberger, Corinna, Schmitz, Gerd, Horsthemke, Bernhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967341/
https://www.ncbi.nlm.nih.gov/pubmed/27478504
http://dx.doi.org/10.1186/s13072-016-0079-z
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author Wallner, Stefan
Schröder, Christopher
Leitão, Elsa
Berulava, Tea
Haak, Claudia
Beißer, Daniela
Rahmann, Sven
Richter, Andreas S.
Manke, Thomas
Bönisch, Ulrike
Arrigoni, Laura
Fröhler, Sebastian
Klironomos, Filippos
Chen, Wei
Rajewsky, Nikolaus
Müller, Fabian
Ebert, Peter
Lengauer, Thomas
Barann, Matthias
Rosenstiel, Philip
Gasparoni, Gilles
Nordström, Karl
Walter, Jörn
Brors, Benedikt
Zipprich, Gideon
Felder, Bärbel
Klein-Hitpass, Ludger
Attenberger, Corinna
Schmitz, Gerd
Horsthemke, Bernhard
author_facet Wallner, Stefan
Schröder, Christopher
Leitão, Elsa
Berulava, Tea
Haak, Claudia
Beißer, Daniela
Rahmann, Sven
Richter, Andreas S.
Manke, Thomas
Bönisch, Ulrike
Arrigoni, Laura
Fröhler, Sebastian
Klironomos, Filippos
Chen, Wei
Rajewsky, Nikolaus
Müller, Fabian
Ebert, Peter
Lengauer, Thomas
Barann, Matthias
Rosenstiel, Philip
Gasparoni, Gilles
Nordström, Karl
Walter, Jörn
Brors, Benedikt
Zipprich, Gideon
Felder, Bärbel
Klein-Hitpass, Ludger
Attenberger, Corinna
Schmitz, Gerd
Horsthemke, Bernhard
author_sort Wallner, Stefan
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0079-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-49673412016-07-31 Epigenetic dynamics of monocyte-to-macrophage differentiation Wallner, Stefan Schröder, Christopher Leitão, Elsa Berulava, Tea Haak, Claudia Beißer, Daniela Rahmann, Sven Richter, Andreas S. Manke, Thomas Bönisch, Ulrike Arrigoni, Laura Fröhler, Sebastian Klironomos, Filippos Chen, Wei Rajewsky, Nikolaus Müller, Fabian Ebert, Peter Lengauer, Thomas Barann, Matthias Rosenstiel, Philip Gasparoni, Gilles Nordström, Karl Walter, Jörn Brors, Benedikt Zipprich, Gideon Felder, Bärbel Klein-Hitpass, Ludger Attenberger, Corinna Schmitz, Gerd Horsthemke, Bernhard Epigenetics Chromatin Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0079-z) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-29 /pmc/articles/PMC4967341/ /pubmed/27478504 http://dx.doi.org/10.1186/s13072-016-0079-z Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wallner, Stefan
Schröder, Christopher
Leitão, Elsa
Berulava, Tea
Haak, Claudia
Beißer, Daniela
Rahmann, Sven
Richter, Andreas S.
Manke, Thomas
Bönisch, Ulrike
Arrigoni, Laura
Fröhler, Sebastian
Klironomos, Filippos
Chen, Wei
Rajewsky, Nikolaus
Müller, Fabian
Ebert, Peter
Lengauer, Thomas
Barann, Matthias
Rosenstiel, Philip
Gasparoni, Gilles
Nordström, Karl
Walter, Jörn
Brors, Benedikt
Zipprich, Gideon
Felder, Bärbel
Klein-Hitpass, Ludger
Attenberger, Corinna
Schmitz, Gerd
Horsthemke, Bernhard
Epigenetic dynamics of monocyte-to-macrophage differentiation
title Epigenetic dynamics of monocyte-to-macrophage differentiation
title_full Epigenetic dynamics of monocyte-to-macrophage differentiation
title_fullStr Epigenetic dynamics of monocyte-to-macrophage differentiation
title_full_unstemmed Epigenetic dynamics of monocyte-to-macrophage differentiation
title_short Epigenetic dynamics of monocyte-to-macrophage differentiation
title_sort epigenetic dynamics of monocyte-to-macrophage differentiation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967341/
https://www.ncbi.nlm.nih.gov/pubmed/27478504
http://dx.doi.org/10.1186/s13072-016-0079-z
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