An atomic model of the interferon-β enhanceosome
An atomic model of the interferon-β enhanceosome
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DOI：
10.1016/j.cell.2007.05.019
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发表时间：
2007-06-15
期刊：
影响因子：
64.5
通讯作者：
Harrison, Stephen C.
中科院分区：
文献类型：
--
作者：
Panne, Daniel;Maniatis, Tom;Harrison, Stephen C.
干扰素- β (ifn - β)基因的转录激活需要一个包含ATF-2/c-Jun、IRF-3/IRF-7和NF κ b的增强体的组装。这些因子与ifn - β增强子协同结合，并将辅助激活因子和染色质重塑蛋白招募到ifn - β启动子上。我们在这里描述了IRF-3、IRF-7和NF κ B的DNA结合域的晶体结构，它们与一半的增强子结合，并使用先前描述的剩余一半的结构来组装DNA附近增强体结构的完整图像。八种蛋白质与增强子的结合创造了一个连续的表面，用于识别复合dna结合元件。局部蛋白-蛋白接触的缺乏表明，增强子的协同占用来自于结合诱导的DNA构象变化和与其他组分（如CBP）的相互作用。与几乎每个核苷酸对的接触解释了增强子序列的进化不变性。
Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceo-some containing ATF-2/c-Jun, IRF-3/IRF-7, and NF kappa B. These factors bind cooperatively to the IFN-beta enhancer and recruit coactivators and chromatin-remodeling proteins to the IFN-beta promoter. We describe here a crystal structure of the DNA-binding domains of IRF-3, IRF-7, and NF kappa B, bound to one half of the enhancer, and use a previously described structure of the remaining half to assemble a complete picture of enhanceosome architecture in the vicinity of the DNA. Association of eight proteins with the enhancer creates a continuous surface for recognizing a composite DNA-binding element. Paucity of local protein-protein contacts suggests that cooperative occupancy of the enhancer comes from both binding-induced changes in DNA conformation and interactions with additional components such as CBP. Contacts with virtually every nucleotide pair account for the evolutionary invariance of the enhancer sequence.