Aso T, Conaway J W, Conaway R C
Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City 73104.
J Biol Chem. 1994 Oct 21;269(42):26575-83.
Efforts to understand the impact of core promoter architecture on the mechanism of transcription initiation by RNA polymerase II have been hampered by lack of well defined, reconstituted transcription systems responsive both to efficiently transcribed consensus and near consensus TATA box-containing promoters and to considerably weaker TATA-less promoters. In this report, we investigate the influence of core promoter structure on the mechanism of assembly of the RNA polymerase II preinitiation complex using a highly purified, holoTFIID-dependent transcription system that permits sensitive measurement of transcription initiation from a wide variety of TATA and TATA-less promoters in the absence of transactivators. A direct comparison of the requirements for formation of stable preinitiation intermediates at these promoters led to the discovery that, whereas holoTFIID binds avidly to the consensus TATA- and strong initiator-containing adenovirus major late (AdML) promoter to form the first stable intermediate on the pathway leading to formation of the complete preinitiation complex, it binds poorly not only to TATA-less promoters but also to promoters with consensus or near consensus TATA elements. With the exception of the AdML promoter, formation of stable preinitiation intermediates at each of the promoters tested was found to be strongly dependent on RNA polymerase II, holoTFIID, and TFIIB and was stimulated by TFIIF. Based on these observations, we suggest that RNA polymerase II assembles with many TATA and TATA-less promoters by a common pathway.
由于缺乏明确的、可重构的转录系统,难以理解核心启动子结构对RNA聚合酶II转录起始机制的影响。这种转录系统既要对高效转录的共有序列和含有接近共有序列TATA框的启动子有反应,也要对弱得多的无TATA框启动子有反应。在本报告中,我们使用高度纯化的、依赖全酶TFIID的转录系统,研究核心启动子结构对RNA聚合酶II起始前复合物组装机制的影响。该系统允许在不存在反式激活因子的情况下,灵敏地测量来自多种TATA框和无TATA框启动子的转录起始。对这些启动子形成稳定起始前中间体的要求进行直接比较后发现,全酶TFIID能 avidly 结合含有共有序列TATA框和强起始子的腺病毒主要晚期(AdML)启动子,在通向形成完整起始前复合物的途径上形成第一个稳定中间体,但它不仅与无TATA框启动子结合不佳,而且与含有共有序列或接近共有序列TATA元件的启动子结合也不佳。除了AdML启动子外,在所测试的每个启动子上,稳定起始前中间体的形成都强烈依赖于RNA聚合酶II、全酶TFIID和TFIIB,并受到TFIIF的刺激。基于这些观察结果,我们认为RNA聚合酶II通过一条共同途径与许多TATA框和无TATA框启动子组装。 (注:avidly这个词原文可能有误,推测可能是avidly,意为“热切地、贪婪地”,这里暂按此翻译,具体需结合原文进一步确认)