The interferon-inducible Stat2:Stat1 heterodimer preferentially binds in vitro to a consensus element found in the promoters of a subset of interferon-stimulated genes
The interferon-inducible Stat2:Stat1 heterodimer preferentially binds in vitro to a consensus element found in the promoters of a subset of interferon-stimulated genes
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DOI：
10.1089/107999001750277853
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发表时间：
2001-06-01
影响因子：
2.3
通讯作者：
Fish, EN
中科院分区：
文献类型：
--
作者：
Ghislain, JJ;Wong, T;Fish, EN
I 型干扰素 (IFN) 刺激基因 (ISG) 的调节表达需要信号转导子和转录激活子 (Stat) 复合物与位于 ISG 启动子中的增强子元件结合。这些增强子元件包括 IFN 刺激反应元件 (ISRE) 和回文 IFN-γ 激活位点 (GAS) 元件。含有 ISG 的 ISRE 的调节表达取决于 IFN 刺激的基因因子 3 (ISGF3)，这是一种涉及 Stat1 和 Stat2 的异二聚体，与 DNA 结合接头蛋白 p48/IFN 调节因子 9 (IRF-9) 相关。已经描述了涉及 Stat1、Stat3、Stat4 和 Stat5 的几种 GAS 结合 Stat 复合物，但它们对 GAS 依赖性 ISG 表达的贡献仍有待确定。我们和其他人之前鉴定了一种 IFN-α 诱导型 Stat2:1 异二聚体，它表现出与 IRF-1 基因的 GAS 元件的结合。这些先前的研究提出了 Stat2:1 可能参与含有 GAS 元件的 ISG 子集的转录激活的可能性。为了解决这个问题，我们进行了 PCR 辅助结合位点选择程序来定义 Stat2:1 识别序列。数据显示，Stat2:1 优先结合与多个 ISG 启动子中发现的共有 GAS 元件相似的回文序列。我们的结果表明，除了涉及 Stat2、Stat1 和 p48 关联的经典复合物形成之外，Stat2:1 异二聚体是响应 IFN 处理而形成的，这可能在某些 ISG 的转录调节中发挥重要作用。
Regulated expression of type I interferon (IFN)-stimulated genes (ISG) requires the binding of the signal transducer and activator of transcription (Stat) complexes to enhancer elements located in the ISG promoters. These enhancer elements include the IFN-stimulated response element (ISRE) and the palindromic IFN-gamma activation site (GAS) element. Regulated expression of ISRE containing ISG depends on IFN-stimulated gene factor 3 (ISGF3), a heterodimer involving Stat1 and Stat2 in association with a DNA-binding adapter protein, p48/IFN regulatory factor-9 (IRF-9), Several GAS binding Stat complexes involving Stat1, Stat3, Stat4, and Stat5 have been described, but their contribution to GAS-dependent ISG expression remains to be established. We and others previously identified an IFN-alpha -inducible Stat2:1 heterodimer that exhibits binding to the GAS element of the IRF-1 gene. These previous studies raise the possibility that Stat2:1 may participate in the transcriptional activation of the subset of ISG containing GAS elements. To address this question, we performed a PCR-assisted binding site selection procedure to define the Stat2:1 recognition sequence. The data reveal that Stat2:1 preferentially binds to a palindromic sequence similar to the consensus GAS element found in the promoter of several ISG, Our results establish that in addition to the classic complex formation involving Stat2, Stat1, and p48 associations, Stat2:1 heterodimers are formed in response to IFN treatment that may play an important role in the transcriptional regulation of certain ISG.