The role of HMG I(Y) in the assembly and function of the IFN-beta enhanceosome.
The role of HMG I(Y) in the assembly and function of the IFN-beta enhanceosome.
复制标题
HMG I(Y) 在 IFN-β 增强体的组装和功能中的作用。
DOI：
10.1093/emboj/18.11.3074
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Thanos,D
中科院分区：
文献类型：
--
作者：
Yie,J;Merika,M;Munshi,N;Chen,G;Thanos,D
人类干扰素-β (IFN-β) 基因的病毒诱导增强子响应病毒感染的转录激活需要组装增强体，该增强体由转录激活子 NF-κB、ATF-2/c-Jun、IRF 和哺乳动物高迁移率族 I (Y)[HMG I (Y)] 的结构蛋白组成。在这里，我们证明了增强体组装的第一步，即 HMG I (Y) 依赖的 NF-κB 和 ATF-2/c-Jun 向增强子的募集，是由 HMG I 的离散区域促进的，并且是由 HMG I (Y) 在 DNA 中诱导的变构变化介导的，而不是由 HMG I (Y) 和这些之间的蛋白质-蛋白质相互作用介导的。 蛋白质。然而，我们发现增强体组装过程的完成需要 HMG I (Y) 和激活剂之间的蛋白质-蛋白质相互作用。最后，我们证明，一旦组装，IFN-β增强体是一种异常稳定的核蛋白结构，可以通过促进多轮转录重新启动来激活高水平的转录。
Transcriptional activation of the virus inducible enhancer of the human interferon‐β (IFN‐β) gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF‐κB, ATF‐2/c‐Jun, IRFs and the architectural protein of the mammalian high mobility group I (Y)[HMG I (Y)]. Here, we demonstrate that the first step in enhanceosome assembly, ie HMG I (Y)‐dependent recruitment of NF‐κB and ATF‐2/c‐Jun to the enhancer, is facilitated by discrete regions of HMG I and is mediated by allosteric changes induced in the DNA by HMG I (Y) and not by protein–protein interactions between HMG I (Y) and these proteins. However, we show that completion of the enhanceosome assembly process requires protein–protein interactions between HMG I (Y) and the activators. Finally, we demonstrate that once assembled, the IFN‐β enhanceosome is an unusually stable nucleoprotein structure that can activate transcription at high levels by promoting multiple rounds of reinitiation of transcription.