...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Target-specific utilization of transcriptional regulatory surfaces by the glucocorticoid receptor
【24h】

Target-specific utilization of transcriptional regulatory surfaces by the glucocorticoid receptor

机译：糖皮质激素受体对转录调控表面的靶标特异性利用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The glucocorticoid receptor (GR) activates or represses transcription depending on the sequence and architecture of the glucocorticoid response elements in target genes and the availability and activity of interacting cofactors. Numerous GR cofactors have been identified, but they alone are insufficient to dictate the specificity of GR action. Furthermdre, the role of different functional surfaces on the receptor itself in regulating its targets is unclear, due in part to the paucity of known target genes. Using DNA microarrays and real-time quantitative PCR, we identified genes transcriptionally activated by GR, in a translation-independent manner, in two human cell lines. We then assessed in U2OS osteosarcoma cells the consequences of individually disrupting three GR domains, the N-terminal activation function (AF) 1, the C-terminal AF2, or the dimer interface, on activation of these genes. We found that GR targets differed in their requirements for AF1 or AF2, and that the dimer interface was dispensable for activation of some genes in each class. Thus, in a single cell type, different GR surfaces were used in a gene-specific manner. These findings have strong implications for the nature of gene response element signaling, the composition and structure of regulatory complexes, and the mechanisms of context-specific transcriptional regulation.
机译：糖皮质激素受体（GR）激活或抑制转录，具体取决于靶基因中糖皮质激素反应元件的序列和结构以及相互作用辅因子的可用性和活性。已经鉴定出许多GR辅助因子，但仅凭它们不足以决定GR动作的特异性。此外，尚不清楚受体自身上不同功能表面在调节其靶标中的作用，这部分是由于已知靶标基因的缺乏所致。使用DNA芯片和实时定量PCR，我们在两个人类细胞系中鉴定了由GR转录激活的基因，其翻译独立性。然后，我们在U2OS骨肉瘤细胞中评估了在这些基因激活后，单独破坏三个GR域，N端激活功能（AF）1，C端AF2或二聚体界面的后果。我们发现GR目标对AF1或AF2的要求不同，并且二聚体界面对于激活每个类别中的某些基因是必不可少的。因此，在单个细胞类型中，以基因特异性方式使用了不同的GR表面。这些发现对基因反应元件信号传导的性质，调控复合物的组成和结构以及特定于上下文的转录调控机制具有重要意义。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号