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Epigenetic dynamics of monocyte to macrophage differentiation

Monocyte to macrophage differentiation involves major biochemical and structural changes in non-dividing cells. 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 isolated by elutriation and differentiated in vitro by addition of MCSF in serum-free medium. We also investigated the effect of loading the macrophages with modified LDL. We found that many mRNAs and miRNAs were significantly up- or downregulated during differentiation. While there was no correlation between gene expression and DNA methylation changes at transcription start sites, we identified a large number of intra- and intergenic regions that rapidly lost DNA methylation, became nucleosome-free and gained histone marks indicative of active enhancers. Loading of macrophages with modified LDL caused gene expression changes, but no chromatin changes. In summary, our results demonstrate that monocyte to macrophage differentiation is associated with rapid, highly targeted epigenetic changes, whereas lipid uptake mainly affects regulatory circuits of soluble factors.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001002201 Illumina HiSeq 2000 8
Publications Citations
Epigenetic dynamics of monocyte-to-macrophage differentiation.
Epigenetics Chromatin 9: 2016 33
Regions of common inter-individual DNA methylation differences in human monocytes: genetic basis and potential function.
Epigenetics Chromatin 10: 2017 37
Increased chromatin accessibility facilitates intron retention in specific cell differentiation states.
Nucleic Acids Res 50: 2022 11563-11579