LncRNA Dnmt3aos regulates Dnmt3a expression leading to aberrant DNA methylation in macrophage polarization
LncRNA Dnmt3aos regulates Dnmt3a expression leading to aberrant DNA methylation in macrophage polarization
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LncRNA Dnmt3aos 调节 Dnmt3a 表达，导致巨噬细胞极化中异常 DNA 甲基化
DOI：
10.1096/fj.201902379r
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发表时间：
2020-02-13
期刊：
影响因子：
4.8
通讯作者：
Lv, Kun
中科院分区：
文献类型：
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作者：
Li, Xueqin;Zhang, Yingying;Lv, Kun
长链非编码RNA（lncRNA）在多种生物学过程中发挥着重要作用。然而，lncRNA在巨噬细胞极化中的作用仍然在很大程度上未被探索。在这项研究中，鉴定了数千种在不同极化的骨髓源性巨噬细胞（BMDM）中差异表达的lncRNA。其中，Dnmt 3aos（DNA methyltransferase 3A，opposite strand）作为已知的lncRNA，位于Dnmt 3a的反义链上。功能实验进一步证实，Dnmt 3aos在M（IL-4）巨噬细胞中高表达，参与Dnmt 3a表达的调节，在巨噬细胞极化中起关键作用。首次采用MeDIP-seq技术检测了Dnmt 3aos敲低组和对照组M（IL-4）巨噬细胞DNA甲基化谱，鉴定了Dnmt 3aos-Dnmt 3a轴介导的DNA甲基化修饰调控的巨噬细胞极化相关基因IFN-γ。我们的研究将有助于丰富我们对巨噬细胞极化机制的认识，并将为巨噬细胞相关疾病的免疫治疗提供新的见解。
Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages (BMDMs). Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization related gene IFN-γ was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization and will provide new insights for immunotherapy in macrophage-associated diseases.