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Epigenetic dynamics of monocyte-to-macrophage differentiation

机译：单核细胞向巨噬细胞分化的表观遗传动力学

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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.
机译：背景单核细胞向巨噬细胞的分化涉及主要的生化和结构变化。为了阐明基因调控变化在此过程中的作用，我们使用了高通量测序来分析人单核细胞的完整转录组和表观基因组，这些无核培养基是通过在无血清培养基中添加集落刺激因子1而在体外分化的。结果大量的mRNA和miRNA被显着上调或下调。十多个11种易位酶将100多个离散的DNA区（通常最远离转录起始位点）迅速脱甲基，变得无核小体，并获得了表明其是活性增强子的组蛋白标记。这些区域对于巨噬细胞而言是独特的，并与参与肌动蛋白细胞骨架，吞噬作用和先天免疫应答调节的基因相关。结论总的来说，我们发现了一个吞噬基因网络，该网络被单核细胞中的DNA甲基化所抑制，并在巨噬细胞分化开始后迅速被抑制。

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