Librizzi M D, Brenowitz M, Willis I M
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Biol Chem. 1998 Feb 20;273(8):4563-8. doi: 10.1074/jbc.273.8.4563.
We have conducted a quantitative thermodynamic study of the effects of the TATA element and TATA-flanking sequences on the assembly of complexes containing TATA-binding protein (TBP) and the TFIIB-related factor, TFIIIB70. TBP binds to the sequence TATAAAAG in the context of the yeast U6 gene (yU6 hybrid TATA) or the adenovirus major late promoter (AdMLP) with different affinities demonstrating that the sequence context of a TATA element contributes to TBP binding. We also determined the cooperative free energies of formation of TBP.TFIIIB70.DNA complexes on the yU6 TATA element, the yU6 hybrid TATA element and a nonconsensus TATA element. The yU6 hybrid TATA displayed a moderate, less than 5-fold, increase in TBP affinity similar to the 3-fold increase observed for the AdMLP. In contrast, the nonconsensus and yU6 TATAs increased the affinity of TBP for DNA 12- and 17-fold, respectively. Since the TBP-TFIIIB70 cooperativity is greater on lower affinity TATA boxes and most polymerase III genes contain low affinity "TATA boxes," we conclude that the cooperative binding of TFIIIB70 and TBP to DNA represents an important driving force in the assembly of polymerase III-specific transcription complexes. An effect of the sequences surrounding the TATA box was also observed on TBP-TFIIIB70 cooperativity. The mechanistic implications of the thermodynamic linkage between DNA sequence and binding cooperativity are discussed.
我们对TATA元件及TATA侧翼序列对包含TATA结合蛋白(TBP)和TFIIB相关因子TFIIIB70的复合物组装的影响进行了定量热力学研究。TBP在酵母U6基因(yU6杂交TATA)或腺病毒主要晚期启动子(AdMLP)的背景下与序列TATAAAAG结合,亲和力不同,这表明TATA元件的序列背景有助于TBP的结合。我们还测定了在yU6 TATA元件、yU6杂交TATA元件和一个非共有TATA元件上TBP.TFIIIB70.DNA复合物形成的协同自由能。yU6杂交TATA显示TBP亲和力有适度增加,不到5倍,类似于在AdMLP中观察到的3倍增加。相比之下,非共有TATA和yU6 TATA分别使TBP对DNA的亲和力增加了12倍和17倍。由于在较低亲和力的TATA框上TBP - TFIIIB70的协同作用更大,并且大多数聚合酶III基因含有低亲和力的“TATA框”,我们得出结论,TFIIIB70和TBP与DNA的协同结合是聚合酶III特异性转录复合物组装中的一个重要驱动力。还观察到TATA框周围序列对TBP - TFIIIB70协同作用的影响。讨论了DNA序列与结合协同性之间热力学联系的机制意义。