Mechanism by which the IFN-beta enhanceosome activates transcription.
Mechanism by which the IFN-beta enhanceosome activates transcription.
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DOI：
10.1073/pnas.96.23.13108
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发表时间：
1999-11
影响因子：
11.1
通讯作者：
J. Yie;K. Senger;D. Thanos
中科院分区：
文献类型：
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作者：
J. Yie;K. Senger;D. Thanos
我们证明，在以前的研究结果相比，通过使用简单的合成启动子或激活剂，天然的IFN-β增强体激活转录引起的速度急剧增加的preinitiation复合物组装在启动子。这种效应完全依赖于增强体对CBP-PolII全酶的募集，因为它从提取物中的消耗会降低转录速率。然而，将CBP-PolII全酶添加回这些提取物完全恢复了增强体激活转录的速度。引人注目的是，增强体与CBP-RNA PolII全酶复合物的预孵育导致preinitiation复合物的即时组装。相比之下，单个IFN-β基因激活剂仅通过增加功能性预起始复合物的数量而不是其组装速率来发挥作用。因此，CBP-RNA PolII全酶复合物的快速募集对于通过病毒感染快速激活IFN-β基因表达是至关重要的。
We demonstrate that in contrast to previous findings by using simple synthetic promoters or activators, the natural IFN-beta enhanceosome activates transcription by causing a dramatic increase of the rate by which preinitiation complexes assemble at the promoter. This effect totally depends on the recruitment of the CBP-PolII holoenzyme by the enhanceosome, because its depletion from the extract decelerates the rate of transcription. However, addition of the CBP-PolII holoenzyme back to these extracts fully restores the speed by which the enhanceosome activates transcription. Strikingly, preincubation of the enhanceosome with the CBP-RNA PolII holoenzyme complex results in instant assembly of preinitiation complexes. In contrast, individual IFN-beta gene activators function solely by increasing the number of functional preinitiation complexes and not the rate of their assembly. Thus, fast recruitment of the CBP-RNA PolII holoenzyme complex is critical for the rapid activation of IFN-beta gene expression by virus infection.