The zinc finger repressor, ZBP-89, recruits histone deacetylase 1 to repress vimentin gene expression
The zinc finger repressor, ZBP-89, recruits histone deacetylase 1 to repress vimentin gene expression
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DOI：
10.1111/j.1365-2443.2007.01104.x
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发表时间：
2007-08-01
期刊：
影响因子：
2.1
通讯作者：
Zehner, Zendra E.
中科院分区：
文献类型：
--
作者：
Wu, Yongzhong;Zhang, Xueping;Zehner, Zendra E.
波形蛋白是中间丝(IF)蛋白家族的成员，具有复杂的组织和发育特异性表达模式。虽然波形蛋白在胚胎中广泛表达，但在终末分化过程中其表达受到限制。此外，它经常在组织培养细胞中表达，尽管它们来自胚胎，并且是转移的肿瘤细胞的标志。此前，波形蛋白启动子已被证明含有几个正负作用的顺式元件。负性元件与转录因子ZBP-结合。有趣的是，ZBP-89既可以是基因表达的激活剂，也可以是抑制物。例如，ZBP-89已被证明通过将p300招募到p21启动子来激活p21(waf1/cip1)的表达。在这里，我们研究了ZBP-89抑制的机制。组蛋白脱乙酰酶(HDAC)抑制剂TSA增强Vimentin基因的表达，需要包括GC-box 1在内的近端启动子区域，GC-box 1是已知的Sp1/SP3结合位点。染色质免疫沉淀(ChIP)分析表明，TSA治疗后，内源性波形蛋白基因上组蛋白H3的乙酰化状态增加。然而，EMSA、DNA沉淀、免疫共沉淀和芯片数据显示，招募HDAC1的不是Sp1，而是ZBP-。根据这些研究，我们得出结论，ZBP-89通过将HDAC1招募到波形蛋白启动子来发挥抑制作用。
Vimentin, a member of the intermediate filament (IF) protein family, exhibits a complex pattern of tissue- and developmental-specific expression. Although vimentin is widely expressed in the embryo, its expression becomes restricted during terminal differentiation. Moreover, it is often expressed in tissue culture cells despite their embryological origin and is a marker for the metastatic tumor cell. Previously, the vimentin promoter has been shown to contain several positive- and negative-acting cis-elements. The negative elements bind the transcription factor ZBP-89. Interestingly, ZBP- 89 can be either an activator or a repressor of gene expression. For instance, ZBP- 89 has been shown to activate p21(waf1/cip1) expression by recruiting p300 to the p2l promoter. Here, we have investigated the mechanism of ZBP-89 repression. The histone deacetylase (HDAC) inhibitor TSA enhances vimentin gene expression requiring the proximal promoter region including GC-box 1, a known Sp1/Sp3 binding site. Chromatin immunoprecipitation (ChIP) assays document an increase in the acetylation status of histone H3 on the endogenous vimentin gene concomitant with TSA treatment. However, EMSAs, DNA precipitation, co-immunoprecipitation and ChIP data show that it is not Sp1, but rather ZBP-89, which recruits HDAC1. From these studies we conclude that ZBP-89 functions as a repressor by recruiting HDAC1 to the vimentin promoter.