A mechanism for coordinating chromatin modification and preinitiation complex assembly
A mechanism for coordinating chromatin modification and preinitiation complex assembly
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DOI：
10.1016/j.molcel.2006.07.018
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发表时间：
2006-09-15
期刊：
影响因子：
16
通讯作者：
Carey, Michael
中科院分区：
文献类型：
--
作者：
Black, Joshua C.;Choi, Janet E.;Carey, Michael
真核基因在染色质环境中的转录需要激活剂依次募集组蛋白修饰酶和通用转录因子（GTF）。然而，这是未知的preinitiation复杂的装配是如何协调与染色质修饰。在这里，我们表明，模型激活剂GAL 4-VP 16指导有序组装介质，组蛋白乙酰转移酶（HAT），和GTF固定染色质和裸DNA模板在体外。使用纯化的蛋白质，我们发现介体通过与p300和TFIID结合来调节该组装过程。乙酰辅酶A依赖性催化开关导致p300乙酰化染色质，然后解离。p300的解离增强TFIID结合和活性转录。解离是由p300催化结构域中的自乙酰化诱导的构象变化引起的。我们的结论是，自乙酰化诱导的p300的解离作为一个催化开关，这使得TFIID绑定和随后的preinitiation复杂的装配。
Transcription of eukaryotic genes within a chromatin environment requires the sequential recruitment of histone modification enzymes and the general transcription factors (GTFs) by activators. However, it is unknown how preinitiation complex assembly is coordinated with chromatin modification. Here, we show that the model activator GAL4-VP16 directs the ordered assembly of Mediator, histone acetyltransferases (HATs), and GTFs onto immobilized chromatin and naked DNA templates in vitro. Using purified proteins, we found that the Mediator regulates this assembly process by binding to p300 and TFIID. An acetyl-CoA-dependent catalytic switch causes p300 to acetylate chromatin and then dissociate. Dissociation of p300 enhances TFIID binding and active transcription. The dissociation is caused by an autoacetylation-induced conformational change in the catalytic domain of p300. We conclude that autoacetylation-induced dissociation of p300 acts as a catalytic switch, which allows TFIID binding and subsequent preinitiation complex assembly.