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Wallner
et al. Epigenetics & Chromatin (2016) 9:33
DOI 10.1186/s13072-016-0079-z
RESEARCH
Epigenetic dynamics of monocyte
-
to
-
macrophage differentiation
Stefan
Wallner
1
, Christopher
Schröder
2
, Elsa
Leitão
3
, Tea
Berulava
3
, Claudia
Haak
3
, Daniela
Beißer
2
,
Sven
Rahmann
2
, Andreas
S.
Richter
4
, Thomas
Manke
4
, Ulrike
Bönisch
4
, Laura
Arrigoni
4
, Sebastian
Fröhler
5
,
Filippos
Klironomos
5
, Wei
Chen
5
, Nikolaus
Rajewsky
5
, Fabian
Müller
6
, Peter
Ebert
6
, Thomas
Lengauer
6
,
Matthias
Barann
7
, Philip
Rosenstiel
7
, Gilles
Gasparoni
8
, Karl
Nordström
8
, Jörn
Walter
8
, Benedikt
Brors
9
,
Gideon
Zipprich
9
, Bärbel
Felder
9
, Ludger
Klein‑Hitpass
10
, Corinna
Attenberger
11
, Gerd
Schmitz
1
and
Bernhard
Horsthemke
3*
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:
Monocyte, Macrophage, Epigenetics, Methylation, Enhancer, Next
‑
generation sequencing, Ten eleven
translocation methylcytosine dioxygenase, TET, DEEP, IHEC
© 2016 The Author(s). This 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.
