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首页> 外文期刊>Molecular and Cellular Biology >Snail Mediates E-Cadherin Repression by the Recruitment of the Sin3A/Histone Deacetylase 1 (HDAC1)/HDAC2 Complex
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Snail Mediates E-Cadherin Repression by the Recruitment of the Sin3A/Histone Deacetylase 1 (HDAC1)/HDAC2 Complex

机译：蜗牛通过招聘Sin3A /组蛋白脱乙酰基酶1（HDAC1）/ HDAC2复合体介导E-钙黏着蛋白抑制。

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摘要

The transcription factor Snail has been described as a direct repressor of E-cadherin expression during development and carcinogenesis; however, the specific mechanisms involved in this process remain largely unknown. Here we show that mammalian Snail requires histone deacetylase (HDAC) activity to repress E-cadherin promoter and that treatment with trichostatin A (TSA) is sufficient to block the repressor effect of Snail. Moreover, overexpression of Snail is correlated with deacetylation of histones H3 and H4 at the E-cadherin promoter, and TSA treatment in Snail-expressing cells reverses the acetylation status of histones. Additionally, we demonstrate that Snail interacts in vivo with the E-cadherin promoter and recruits HDAC activity. Most importantly, we demonstrate an interaction between Snail, histone deacetylase 1 (HDAC1) and HDAC2, and the corepressor mSin3A. This interaction is dependent on the SNAG domain of Snail, indicating that the Snail transcription factor mediates the repression by recruitment of chromatin-modifying activities, forming a multimolecular complex to repress E-cadherin expression. Our results establish a direct causal relationship between Snail-dependent repression of E-cadherin and the modification of chromatin at its promoter.
机译：转录因子Snail被描述为在发育和致癌过程中E-钙粘蛋白表达的直接阻遏物。但是，此过程中涉及的具体机制仍然未知。在这里，我们显示哺乳动物Snail需要组蛋白脱乙酰基酶（HDAC）活性来抑制E-钙粘蛋白启动子，而曲古抑菌素A（TSA）的治疗足以阻止Snail的阻遏作用。此外，Snail的过表达与E-cadherin启动子上组蛋白H3和H4的去乙酰化有关，TSA处理在表达Snail的细胞中逆转了组蛋白的乙酰化状态。此外，我们证明了Snail在体内与E-cadherin启动子相互作用并募集HDAC活性。最重要的是，我们证明了Snail，组蛋白脱乙酰基酶1（HDAC1）和HDAC2与共抑制因子mSin3A之间的相互作用。这种相互作用取决于Snail的SNAG结构域，表明Snail转录因子通过募集染色质修饰活性来介导阻遏作用，形成抑制E-钙粘蛋白表达的多分子复合物。我们的研究结果建立了Snail依赖性E-钙粘蛋白抑制与启动子染色质修饰之间的直接因果关系。

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