TFIIA regulates TBP and TFIID dimers

TFIIA regulates TBP and TFIID dimers
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DOI:
10.1016/s1097-2765(00)80453-0
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发表时间:
1999-09-01
期刊:
影响因子:
16
通讯作者:
Pugh, BF
Pugh, BF
中科院分区:
生物学1区
文献类型:
--
作者:
Coleman, RA;Taggart, AKP;Pugh, BF

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TATA结合蛋白(TBP)通过其DNA结合结构域的二聚化阻止TBP进入DNA并防止不受调控的基因表达。TFIIA在将TBP及其多亚基对应物TFIID加载到启动子DNA上中起核心作用,因此它是调节TBP/TFIID二聚化的候选物。在这里,我们表明,TFIIA直接促进TBP二聚体的解离,并在这样做加速了DNA结合的动力学。发现TFIID二聚体解离在DNA结合中是缓慢的和速率限制的。TFIIA诱导TFIID二聚体的快速解离,使得TFIID容易地加载到启动子DNA上。总之,这些结果表明一种新的机制,TFIIA协助调节基因表达。
Dimerization of the TATA-binding protein (TBP) through its DNA-binding domain blocks TBP from accessing DNA and prevents unregulated gene expression. TFIIA plays a central role in loading TBP and its multisubunit counterpart TFIID onto promoter DNA, and it is therefore a candidate for regulating TBP/TFIID dimerization. Here, we show that TFIIA promotes the dissociation of TBP dimers directly and in doing so accelerates the kinetics of DNA binding. TFIID dimer dissociation was found to be slow and rate limiting in DNA binding. TFIIA induced a rapid dissociation of TFIID dimers, allowing TFIID to readily load onto promoter DNA. Together, these results suggest a novel mechanism by which TFIIA assists in regulating gene expression.