RNA POLYMERASE 11 TRANSCRIPTIONAL REGULATION IN DROSOPHILA

RNA聚合酶II指导蛋白质编码基因的转录 通过一种多蛋白复合物，包括基因特异性增强子结合 因子和基础转录因子（TFIIA，TFIIB，TFIID，TFIIE， TFIIF和TFIIH）。 在体外，基础转录因子足够 从核心启动子引导低水平转录，但增强子 需要结合因子及其DNA结合位点来实现 更高水平的转录，称为激活或调节 转录。 蛋白质之间的相互作用激活 增强子结合因子的结构域和TFIID的一个或多个亚基 介导体外激活转录。 TFIID是一种多蛋白 由TATA结合蛋白（TBP）和至少八个 TBP相关因子（TAF）。 特定TAF结合不同类型的 活化剂（如酸性的、富含谷氨酰胺的或富含异亮氨酸的）。 在 此外，TAF与转录机器的其它组分接触， 识别和接触核心启动子中的特异性DNA序列，并具有 可能有助于基因特异性转录的酶活性 体内激活。 我们在几种果蝇中分离出突变 TAF在筛选显性修饰粗糙眼表型的基因中的应用 由表达Ras 1功能获得型的转基因引起 好的 TAF突变降低Ras 1基因的转录水平 转基因以及从其他但不是全部RNA的转录 聚合酶II基因。 果蝇最初被选为模型 研究TFIID和TAFs在转录调控中的作用。 调节，因为它是服从生化，分子和遗传 方法，它显示了复杂的发育和组织特异性 转录调控 这种致敏基因的建立 系统在果蝇提供了机会，探测在体内的作用， TAFs，并结合TAFs的丰富生化数据， 破译控制转录激活的分子机制。

Transcription of protein coding genes by RNA polymerase II is directed by a multiprotein complex that includes gene-specific enhancer binding factors and basal transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH). In vitro, basal transcription factors are sufficient to direct a low level of transcription from a core promoter, but enhancer binding factors and their DNA binding sites are required to achieve a higher level of transcription, termed activated or regulated transcription. Protein-protein interactions between the activation domains of enhancer binding factors and one or more subunits of TFIID mediate activated transcription in vitro. TFIID is a multiprotein complex composed of TATA-binding protein (TBP) and at least eight TBP-associated factors (TAFs). Specific TAFs bind different classes of activators (such as acidic, glutamine rich, or isoleucine rich). In addition, TAFs contact other components of the transcriptional machinery, recognize and contact specific DNA sequences in core promoters, and have enzymatic activities that may contribute to gene-specific transcriptional activation in vivo. We have isolated mutations in several Drosophila TAFs in a screen for genes that dominantly modify a rough eye phenotype caused by a transgene expressing a gain-of-function form of the Ras1 GTPase. TAF mutations reduce the level of transcription of the Ras1 transgene as well as transcription from other, but not all, RNA polymerase II genes. Drosophila was originally chosen as the model organism to study the role of TFIID and TAFs in transcriptional regulation because it is amenable to biochemical, molecular, and genetic approaches, and it displays complex developmental and tissue-specific transcriptional regulation. The establishment of this sensitized genetic system in Drosophila presents the opportunity to probe in vivo roles for TAFs and, in combination with the wealth of biochemical data on TAFs, to decipher the molecular mechanisms controlling transcriptional activation.