Global mapping of H3K4me3 and H3K27me3 reveals chromatin state-based regulation of human monocyte-derived dendritic cells in different environments
Global mapping of H3K4me3 and H3K27me3 reveals chromatin state-based regulation of human monocyte-derived dendritic cells in different environments
复制标题
H3K4me3 和 H3K27me3 的全局作图揭示了不同环境中人类单核细胞来源的树突状细胞基于染色质状态的调节
DOI：
10.1038/gene.2011.87
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发表时间：
2012-06-01
影响因子：
5
通讯作者：
Yang, R.
中科院分区：
文献类型：
--
作者：
Huang, Y.;Min, S.;Yang, R.
根据环境的不同，树突状细胞（DC）可能会变得活跃或耐受性，但很少有人知道是否遗传表观遗传修饰参与这些过程。在这里，我们发现表观遗传组蛋白修饰可以调节人单核细胞来源的DC（moDC）分化为活化的或耐受的DC。甲基转移酶或甲基化相关因子的抑制或沉默影响多个基因的表达。转化生长因子（TGF-β）-或脂多糖（LPS）-相关的H3 K4三甲基化（H3 K4 me 3）和H3 K27三甲基化（H3 K27 me 3）的基因组作图证明了在人TGF-β-或LPS-条件的moDC中存在基因表达的组蛋白修饰。尽管上调或下调的基因并不总是与TGF-β-条件化（耐受化）或LPS-条件化（活化）的moDC中的H3 K4 me 3和/或H3 K27 me 3修饰相关，但这些基因中的一些可能通过增加和/或降低的H3 K4 me 3或H3 K27 me 3水平或通过这些表观遗传标记的改变来调节，特别是在TGF-β-条件化的moDC中。因此，我们的研究结果表明，moDC在肿瘤和炎症环境中的分化和功能与H3 K4 me 3和K3 K27 me 3表观遗传标记的修饰相关。
Depending on the environment, dendritic cells (DCs) may become active or tolerogenic, but little is known about whether heritable epigenetic modifications are involved in these processes. Here, we have found that epigenetic histone modifications can regulate the differentiation of human monocyte-derived DCs (moDCs) into either activated or tolerized DCs. The inhibition or silencing of methyltransferases or methylation-associated factors affects the expression of multiple genes. Genome mapping of transforming growth factor (TGF-β)-or lipopolysaccharide (LPS)-associated H3K4 trimethylation (H3K4me3) and H3K27 trimethylation (H3K27me3) demonstrated the presence of histone modification of gene expression in human TGF-β-or LPS-conditioned moDCs. Although the upregulated or downregulated genes were not always associated with H3K4me3 and/or H3K27me3 modifications in TGF-β-conditioned (tolerized) or LPS-conditioned (activated) moDCs, some of these genes may be regulated by the increased and/or decreased H3K4me3 or H3K27me3 levels or by the alteration of these epigenetic marks, especially in TGF-β-conditioned moDCs. Thus, our results suggested that the differentiation and function of moDCs in tumor and inflammation environments are associated with the modification of the H3K4me3 and K3K27me3 epigenetic marks.