Martinez E, Zhou Q, L'Etoile N D, Oelgeschläger T, Berk A J, Roeder R G
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11864-8. doi: 10.1073/pnas.92.25.11864.
In conjunction with other general initiation factors, the TATA box-binding protein (TBP) can direct basal transcription by RNA polymerase II from TATA-containing promoters, but its stable interaction with TBP-associated factors (TAFs) in the TFIID complex is required both for activator-dependent transcription and for basal transcription directed by an initiator element. We have generated a TATA-binding-defective TFIID complex containing an amino acid substitution in the DNA-binding surface of its TBP subunit. This mutated TFIID is defective in both basal and activated transcription from core promoters containing only a TATA box but supports transcription from initiator-containing promoters independently of the presence or absence of a TATA sequence. Our results show that a functional initiator element is needed to bypass the requirement for an active TATA DNA-binding surface in TFIID and imply that gene-specific transcription can be achieved by modulating distinct core promoter-specific TFIID functions--e.g., TBP-TATA versus TAF-initiator interactions.
TATA 框结合蛋白(TBP)与其他一般起始因子协同作用时,可通过 RNA 聚合酶 II 从含 TATA 的启动子指导基础转录,但它在 TFIID 复合物中与 TBP 相关因子(TAFs)的稳定相互作用对于激活剂依赖性转录以及由起始子元件指导的基础转录都是必需的。我们构建了一种 TATA 结合缺陷型 TFIID 复合物,其 TBP 亚基的 DNA 结合表面存在氨基酸替换。这种突变的 TFIID 在仅含 TATA 框的核心启动子的基础转录和激活转录中均有缺陷,但无论 TATA 序列是否存在,都能支持含起始子的启动子的转录。我们的结果表明,需要一个功能性的起始子元件来绕过 TFIID 中活性 TATA DNA 结合表面的需求,并暗示通过调节不同的核心启动子特异性 TFIID 功能,如 TBP - TATA 与 TAF - 起始子相互作用,可以实现基因特异性转录。