Up-regulation of IRF-3 expression through GATA-1 acetylation by histone deacetylase inhibitor in lung adenocarcinoma A549 cells.
Up-regulation of IRF-3 expression through GATA-1 acetylation by histone deacetylase inhibitor in lung adenocarcinoma A549 cells.
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组蛋白脱乙酰酶抑制剂通过 GATA-1 乙酰化上调肺腺癌 A549 细胞中 IRF-3 的表达
DOI：
10.18632/oncotarget.18371
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发表时间：
2017-09-29
期刊：
影响因子：
--
通讯作者：
Zhou GP
中科院分区：
文献类型：
--
作者：
Wang LL;Zhou LB;Shu J;Li NN;Zhang HW;Jin R;Zhuang LL;Zhou GP
干扰素调节因子3（IRF-3）是干扰素基因的重要转录因子。尽管病毒感染激活IRF-3基因的功能已被广泛阐明，但对IRF-3基因在癌细胞中表达的调控机制知之甚少。在这项研究中，我们证明了治疗肺腺癌A549细胞与阿司他丁A（TSA）和丙戊酸（VPA），两种不同类别的组蛋白去乙酰化酶抑制剂，强烈刺激IRF-3基因的表达。IRF-3启动子的截短和突变表明，一个特定的加塔-1元件负责TSA诱导的IRF-3启动子的激活。染色质免疫沉淀和电泳迁移率变动分析表明TSA处理增加了加塔-1与IRF-3启动子的结合亲和力。利用免疫沉淀和免疫印迹技术，我们证明TSA增加了A549细胞中乙酰化加塔-1的水平。综上所述，我们的研究表明TSA通过增加肺腺癌A549细胞中加塔-1向IRF-3启动子的募集和加塔-1的乙酰化水平来增强IRF-3基因的表达。
Interferon regulatory factor 3 (IRF-3) is an important transcription factor for interferon genes. Although its functional activation by viral infection has been widely explicated, the regulatory mechanism of IRF-3 gene expression in cancer cells is poorly understood. In this study, we demonstrated treatment of lung adenocarcinoma A549 cells with trichostatin A (TSA) and valproic acid (VPA), two different classes of histone deacetylase inhibitors, strongly stimulated IRF-3 gene expression. Truncated and mutated IRF-3 promoter indicated that a specific GATA-1 element was responsible for TSA-induced activation of IRF-3 promoter. Chromatin immunoprecipitation and electrophoretic mobility shift assay showed that TSA treatment increased the binding affinity of GATA-1 to IRF-3 promoter. Using immunoprecipitation assay and immunoblotting, we demonstrated that TSA increased the level of acetylated GATA-1 in A549 cells. In summary, our study implied that TSA enhanced IRF-3 gene expression through increased GATA-1 recruitment to IRF-3 promoter and the acetylation level of GATA-1 in lung adenocarcinoma A549 cells.
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