Transcriptional induction of DLC-1 gene through Sp1 sites by histone deacetylase inhibitors in gastric cancer cells
Transcriptional induction of DLC-1 gene through Sp1 sites by histone deacetylase inhibitors in gastric cancer cells
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DOI：
10.3858/emm.2008.40.6.639
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发表时间：
2008-12-31
影响因子：
12.8
通讯作者：
Bang, Yung-Jue
中科院分区：
文献类型：
--
作者：
Kim, Tai Young;Kim, In Sook;Bang, Yung-Jue
我们先前报道了组蛋白去乙酰化酶（HDAC）抑制剂阿司他汀A（TSA）诱导DLC-1 mRNA表达，并在DLC-1非表达胃癌细胞中积累与DLC-1启动子相关的乙酰化组蛋白H3和H4。在这项研究中，我们证明了TSA诱导DLC-1基因表达的分子机制。用TSA处理胃癌细胞通过位于相对于转录起始位点的-219和-174的Sp1位点激活DLC-1启动子活性。电泳迁移率变动分析（EMSA）显示，Sp1和Sp3特异性地与这些Sp1位点相互作用，并显示TSA没有改变它们的结合活性。Sp1而非Sp3的异位表达增强了TSA对DLC-1启动子的响应性。此外，TSA诱导的DLC-1启动子活性通过p300表达而增加，通过p300敲低而降低。这些结果表明，特异性Sp1位点的需求和Sp1和p300的依赖性TSA介导的激活DLC-1启动子。
We previously reported that trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, induced DLC-1 mRNA expression and accumulated acetylated histones H3 and H4 associated with the DLC-1 promoter in DLC-1 non-expressing gastric cancer cells. In this study, we demonstrated the molecular mechanisms by which TSA induced the DLC-1 gene expression. Treatment of the gastric cancer cells with TSA activates the DLC-1 promoter activity through Sp1 sites located at -219 and -174 relative to the transcription start site. Electrophoretic mobility-shift assay (EMSA) revealed that Sp1 and Sp3 specifically interact with these Sp1 sites and showed that TSA did not change their binding activities. The ectopic expression of Sp1, but not Sp3, enhances the DLC-1 promoter responsiveness by TSA. Furthermore, the TSA-induced DLC-1 promoter activity was increased by p300 expression and reduced by knockdown of p300. These results demonstrated the requirement of specific Sp1 sites and dependence of Sp1 and p300 for TSA-mediated activation of DLC-1 promoter.