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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Apical role for BRG1 in cytokine-induced promoter assembly.
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Apical role for BRG1 in cytokine-induced promoter assembly.

机译：BRG1在细胞因子诱导的启动子装配中的重要作用。

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摘要

IFN-gamma induction of the CIITA (class II transactivator) promoter (pIV) requires Brahma-related gene 1 (BRG1), a chromatin-remodeling enzyme. However, the events that lead to pIV activation are only partially understood, and the point at which BRG1 acts is unknown. The first IFN-gamma-induced event triggers nuclear translocation of STAT1 (signal transducer and activator of transcription 1), which binds IFN-gamma-responsive promoters. BRG1 is recruited after activator binding at several other inducible loci, and STAT family members are known to bind BRG1, suggesting that BRG1 might act downstream of STAT1. Here, we delineate a comprehensive view of factor assembly and detailed histone modifications at pIV and show that all events, even STAT1 binding, require BRG1 at CIITA pIV and other IFN-gamma target promoters. Recruitment of IFN-stimulated gene factor-3 (ISGF3) [STAT1/STAT2/IFN regulatory factor 9 (IRF9)] to several IFN-alpha-responsive promoters is also BRG1-dependent. In contrast, constitutive BRG1 association at IFN targets is STAT1-independent. Furthermore, BRG1 is required for IFN-induced restriction enzyme and DNase I accessibility at promoters. Thus, BRG1 has an apical role in cytokine-induced promoter assembly, acting upstream of STAT complexes at multiple IFN target loci.
机译：CIITA（II类反式激活子）启动子（pIV）的IFN-γ诱导需要梵天相关基因1（BRG1），一种染色质重塑酶。但是，导致pIV激活的事件仅被部分理解，BRG1作用的时间点尚不清楚。第一个由IFN-γ诱导的事件触发STAT1的核易位（信号转导和转录激活因子1），它与IFN-γ响应的启动子结合。在激活剂结合到其他几个可诱导基因座后，BRG1被募集，并且已知STAT家族成员结合BRG1，这表明BRG1可能在STAT1的下游起作用。在这里，我们描绘了因子装配的全面视图和pIV处的详细组蛋白修饰，并显示所有事件，甚至STAT1结合，都需要CIITA pIV处的BRG1和其他IFN-γ靶标启动子。 IFN刺激的基因因子3（ISGF3）[STAT1 / STAT2 / IFN调节因子9（IRF9）]的招募也依赖于BRG1。相反，在IFN靶标上的本构BRG1缔合是STAT1非依赖性的。此外，BRG1是启动子中IFN诱导的限制性酶和DNase I可及性所必需的。因此，BRG1在细胞因子诱导的启动子装配中具有顶峰作用，在多个IFN靶基因座的STAT复合物上游起作用。

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