The transcription repressor, ZEB1, cooperates with CtBP2 and HDAC1 to suppress IL-2 gene activation in T cells
The transcription repressor, ZEB1, cooperates with CtBP2 and HDAC1 to suppress IL-2 gene activation in T cells
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DOI：
10.1093/intimm/dxn143
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Shannon, M. Frances
中科院分区：
文献类型：
--
作者：
Wang, Jun;Lee, Seungsoo;Shannon, M. Frances
T细胞的活化导致诱导适当免疫应答所需的许多细胞因子基因，包括IL-2，T细胞增殖和稳态的关键细胞因子。转录激活因子如活化T细胞的核因子、核因子κ B/Rel和活化蛋白1家族成员调节诱导型IL-2基因表达已被充分证明。然而，IL-2基因的负调控研究较少。在这里，我们研究锌指E-box结合蛋白（ZEB）1，同源结构域/锌指转录因子，作为IL-2基因转录的阻遏物的作用。我们在这里表明，ZEB 1在非刺激和刺激的T细胞中表达，并使用染色质免疫沉淀试验，我们表明，ZEB 1结合IL-2启动子。ZEB 1的过表达可以抑制IL-2启动子活性，以及EL-4 T细胞中内源性IL-2 mRNA的产生，并且这种抑制依赖于-100处的ZEB结合位点。ZEB 1与辅阻遏物C-末端结合蛋白（CtBP）2和组蛋白脱乙酰基酶1合作以抑制IL-2启动子，这种合作依赖于启动子中的ZEB结合位点以及CtBP 2中的Pro-X-Asp-Leu-Ser蛋白-蛋白相互作用结构域。因此，ZEB 1可以发挥功能以将阻遏物复合物募集到IL-2启动子。
Activation of T cells leads to the induction of many cytokine genes that are required for appropriate immune responses, including IL-2, a key cytokine for T cell proliferation and homeostasis. The activating transcription factors such as nuclear factor of activated T cells, nuclear factor kappa B/Rel and activated protein-1 family members that regulate inducible IL-2 gene expression have been well documented. However, negative regulation of the IL-2 gene is less studied. Here we examine the role of zinc finger E-box-binding protein (ZEB) 1, a homeodomain/Zn finger transcription factor, as a repressor of IL-2 gene transcription. We show here that ZEB1 is expressed in non-stimulated and stimulated T cells and using chromatin immunoprecipitation assays we show that ZEB1 binds to the IL-2 promoter. Over-expression of ZEB1 can repress IL-2 promoter activity, as well as endogenous IL-2 mRNA production in EL-4 T cells, and this repression is dependent on the ZEB-binding site at -100. ZEB1 cooperates with the co-repressor C-terminal-binding protein (CtBP) 2 and with histone deacetylase 1 to repress the IL-2 promoter and this cooperation depends on the ZEB-binding site in the promoter as well as the Pro-X-Asp-Leu-Ser protein-protein interaction domain in CtBP2. Thus, ZEB1 may function to recruit a repressor complex to the IL-2 promoter.