Hoffman A, Sinn E, Yamamoto T, Wang J, Roy A, Horikoshi M, Roeder R G
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021.
Nature. 1990 Jul 26;346(6282):387-90. doi: 10.1038/346387a0.
The factor TFIID is one of several general factors that are necessary and sufficient for transcription initiation by mammalian RNA polymerase II. Stable interactions with the common TATA element lead both to template commitment and to the assembly of the other general factors into a functional preinitiation complex. Consistent with its key role in the promoter activation pathway, human TFIID also seems to be a target for some regulatory factors, as evidenced both by physical and functional studies of interactions between these components. The evolutionary conservation of functional properties led to the purification and cloning of yeast TFIID, the identification of presumptive structural motifs, and direct structure-function studies. Here we report the cloning of a complementary DNA encoding a functional human TFIID. This reveals an evolutionarily conserved core which corresponds precisely to the 180-residue DNA binding/activation domain determined for yeast TFIID, a near absolute conservation of component structural motifs (direct repeats, central basic core/lysine repeat, and sigma homology), providing further support for their functional importance, and a unique N-terminal structure that suggests involvement in species-specific regulatory factor interactions.
TFIID因子是哺乳动物RNA聚合酶II转录起始所必需且充分的几种通用因子之一。与常见的TATA元件的稳定相互作用既导致模板确定，也导致其他通用因子组装成功能性的起始前复合物。鉴于其在启动子激活途径中的关键作用，人类TFIID似乎也是一些调节因子的作用靶点，这些成分之间相互作用的物理和功能研究都证明了这一点。功能特性的进化保守性导致了酵母TFIID的纯化和克隆、推定结构基序的鉴定以及直接的结构-功能研究。在此，我们报告了编码功能性人类TFIID的互补DNA的克隆。这揭示了一个进化上保守的核心，它与为酵母TFIID确定的180个残基的DNA结合/激活结构域精确对应，成分结构基序（直接重复、中央碱性核心/赖氨酸重复和sigma同源性）几乎完全保守，这进一步支持了它们的功能重要性，以及一个独特的N端结构，表明其参与物种特异性调节因子的相互作用。
