The Histone Variant H2A.Z Is a Master Regulator of the Epithelial-Mesenchymal Transition
The Histone Variant H2A.Z Is a Master Regulator of the Epithelial-Mesenchymal Transition
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DOI：
10.1016/j.celrep.2017.09.086
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发表时间：
2017-10-24
期刊：
影响因子：
8.8
通讯作者：
Tremethick, David J.
中科院分区：
文献类型：
--
作者：
Domaschenz, Renae;Kurscheid, Sebastian;Tremethick, David J.
上皮间质转化（EMT）是细胞可塑性的一个深刻例子，对于胚胎发育和癌症至关重要。尽管长期以来人们一直怀疑基于染色质的机制在此过程中发挥作用，但迄今为止尚未确定可以特异性调节 EMT 的主调节因子。在这里，我们展示了 H2A。 Z 可以分别作为上皮或间质基因表达的激活剂或阻遏剂来协调 EMT。在 TGF-b 诱导 EMT 后，我们观察到 H2A 意外丢失。 Z 横跨上调的上皮启动子和上调的间质启动子。引人注目的是，上皮基因表达的抑制与 H2A 的减少有关。 Z 位于转录起始位点 (TSS) 上游，而间充质基因表达的激活依赖于 H2A 的去除。 TSS 下游的 Z。因此，H2A的能力。 Z 调节 EMT 取决于其位置，是 TSS 的上游还是下游。
Epithelial-mesenchymal transition (EMT) is a profound example of cell plasticity that is crucial for embryonic development and cancer. Although it has long been suspected that chromatin-based mechanisms play a role in this process, no master regulator that can specifically regulate EMT has been identified to date. Here, we show that H2A. Z can coordinate EMT by serving as either an activator or repressor of epithelial or mesenchymal gene expression, respectively. Following induction of EMT by TGF-b, we observed an unexpected loss of H2A. Z across both downregulated epithelial and upregulated mesenchymal promoters. Strikingly, the repression of epithelial gene expression was associated with reduction of H2A. Z upstream of the transcription start site (TSS), while the activation of mesenchymal gene expression was dependent on removal of H2A. Z downstream of the TSS. Therefore, the ability of H2A. Z to regulate EMT is dependent on its position, either upstream or downstream of the TSS.