Epithelial-mesenchymal transition (EMT) is an important process triggered during cancer metastasis. Regulation of EMT is mostly initiated by outside signalling, including TGF-β, growth factors, Notch ligand, Wnt, and hypoxia. Many signalling pathways have been delineated to explain the molecular mechanisms of EMT. In this review, we will focus on the epigenetic regulation of two critical EMT signalling pathways: hypoxia and TGF-β. For hypoxia, hypoxia-induced EMT is mediated by the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5 coupled with the presence of histone 3 lysine 4 acetylation (H3K4Ac) mark that labels the promoter regions of various traditional EMT marker genes (e.g. CDH1, VIM). Recently identified new hypoxia-induced EMT markers belong to transcription factors (e.g. SMO, GLI1) that mediate EMT themselves. For TGF-β-induced ΕΜΤ, global chromatin changes, removal of a histone variant (H2A.Z), and new chromatin modifiers (e.g. UTX, Rad21, PRMT5, RbBP5, etc) are identified to be crucial for the regulation of both EMT transcription factors (EMT-TFs) and EMT markers (EMT-Ms). The epigenetic mechanisms utilized in these two pathways may serve as good model systems for other signalling pathways and also provide new potential therapeutic targets.

中文翻译：

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上皮-间质转化的表观遗传调控：专注于缺氧和TGF-β信号传导

上皮-间质转化（EMT）是癌症转移过程中触发的重要过程。EMT的调节主要由外部信号启动，包括TGF-β，生长因子，Notch配体，Wnt和缺氧。已经描述了许多信号通路来解释EMT的分子机制。在这篇综述中，我们将集中于两个关键的EMT信号通路的表观遗传调控：缺氧和TGF-β。对于缺氧，缺氧诱导的EMT由染色质修饰剂组蛋白脱乙酰基酶3（HDAC3）和WDR5之间的相互作用介导，并伴随着组蛋白3赖氨酸4乙酰化（H3K4Ac）标记的存在，后者标记了各种传统EMT标记基因的启动子区域（例如CDH1，VIM）。最近发现的新的低氧诱导的EMT标记属于介导EMT自身的转录因子（例如SMO，GLI1）。对于TGF-β诱导的ＥＭＴ，整体染色质变化，组蛋白变体（H2A.Z）的去除和新的染色质修饰剂（例如UTX，Rad21，PRMT5，RbBP5等）被认为对于EMT的调节至关重要转录因子（EMT-TFs）和EMT标记（EMT-Ms）。在这两个途径中利用的表观遗传机制可以作为其他信号途径的良好模型系统，并提供新的潜在治疗靶点。