Epigenetic dynamics of monocyte-to-macrophage differentiation

Abstract

BackgroundMonocyte-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.ResultsNumerous 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.ConclusionsIn 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 materialThe online version of this article (doi:10.1186/s13072-016-0079-z) contains supplementary material, which is available to authorized users.

5-Hydroxymethylcytosine (5hmC), or How to Identify Your Favorite Cell

“…This is the case for Tet2 (and to a lesser degree Tet3), which is consistently reported in murine models [39,40,43,[45][46][47]49] and human cells [37,38,42,[50][51][52]. Of note, the role of Tet2 in mast cell differentiation described above [40] is partially independent of 5hmC, as rescuing mast cell developmental changes upon Tet2 knockout was only possible by the re-expression of Tet2 independently of its catalytic activity, which assumes that Tet2 possibly interacts with other complexes (something similar has been shown between TET1 and the SIN3A co-repressor complex [53]).…”

“…In addition to mast cells, specific redistribution of 5hmC has been described during differentiation of monocytes into macrophages or into dendritic cells [50,51]. Moreover, a unique role of 5hmC in red blood cell development seems well established according to a study that provided a comprehensive view of 5hmC distribution at stem/early progenitors, primitive erythroid progenitors, basophilic, polychromatic, orthochromatic, and reticulocytes [42].…”

TET-Catalyzed 5-Hydroxymethylation Precedes HNF4A Promoter Choice during Differentiation of Bipotent Liver Progenitors

“…Therefore, modulation of 5hmC through interaction with TET proteins may represent a general mechanism of pioneer TFs. In line with this, and in addition to its well-known role in neural development (Santiago et al., 2014, Sun et al., 2014b), 5hmC and/or TETs have been recently implicated in key steps of terminal differentiation such as monocyte-to-macrophage differentiation (Wallner et al., 2016), specification of CD4 T cells (Nestor et al., 2016), cardiomyocyte development (Greco et al., 2016), and colonocyte differentiation (Chapman et al., 2015). …”

Epigenetics in rheumatoid arthritis; fibroblast‐like synoviocytes as an emerging paradigm in the pathogenesis of the disease

“…The active DNA demethylation pathway is dependent on Ten‐eleven translocation enzymes. However, in contrast to their roles in macrophage differentiation, their importance in FLSs has not been demonstrated yet.…”