Polycomb complex 2 is required for E-cadherin repression by the snail1 transcription factor
Polycomb complex 2 is required for E-cadherin repression by the snail1 transcription factor
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DOI：
10.1128/mcb.00323-08
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发表时间：
2008-08-01
影响因子：
5.3
通讯作者：
Peiro, Sandra
中科院分区：
文献类型：
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作者：
Herranz, Nicolas;Pasini, Diego;Peiro, Sandra
转录因子Snail 1是E-cadherin（CDH 1）基因表达的阻遏物，其对于触发上皮-间质转化至关重要。Snail 1抑制CDH 1，直接结合其启动子并诱导Zeb 1阻遏物的合成。在这篇文章中，我们表明，镇压CDH 1蜗牛1，而不是由Zeb 1，是依赖于Polycomb抑制复合物2（PRC 2）的活动。不含PRC 2组分之一Suz 12的胚胎干（ES）细胞显示出比对照ES细胞更高水平的Cdh 1 mRNA。在肿瘤细胞中，PRC 2活性的干扰阻止了Snail 1下调CDH 1的能力，并部分解除了CDH 1的抑制。染色质免疫沉淀分析表明，蜗牛1增加了结合的Suz 12的CDH 1启动子，和组蛋白H3的赖氨酸27的三甲基化。此外，蜗牛1与Suz 12和Ezh 2相互作用，如免疫共沉淀实验所示。总之，这些结果表明，蜗牛招募PRC 2的CDH 1启动子，并需要这个复合物的活性抑制E-钙粘蛋白的表达。
The transcriptional factor Snail1 is a repressor of E-cadherin (CDH1) gene expression essential for triggering epithelial-mesenchymal transition. Snail1 represses CDH1, directly binding its promoter and inducing the synthesis of the Zeb1 repressor. In this article, we show that repression of CDH1 by Snail1, but not by Zeb1, is dependent on the activity of Polycomb repressive complex 2 (PRC2). Embryonic stem (ES) cells null for Suz12, one of the components of PRC2, show higher levels of Cdh1 mRNA than control ES cells. In tumor cells, interference of PRC2 activity prevents the ability of Snail1 to downregulate CDH1 and partially derepresses CDH1. Chromatin immunoprecipitation assays demonstrated that Snail1 increases the binding of Suz12 to the CDH1 promoter, and the trimethylation of lysine 27 in histone H3. Moreover, Snail1 interacts with Suz12 and Ezh2, as shown by coimmunoprecipitation experiments. In conclusion, these results demonstrate that Snail1 recruits PRC2 to the CDH1 promoter and requires the activity of this complex to repress E-cadherin expression.