Liu Wei-Li, Coleman Robert A, Grob Patricia, King David S, Florens Laurence, Washburn Michael P, Geles Kenneth G, Yang Joyce L, Ramey Vincent, Nogales Eva, Tjian Robert
Howard Hughes Medical Institute, Li Ka-Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, CA 94720, USA.
Mol Cell. 2008 Jan 18;29(1):81-91. doi: 10.1016/j.molcel.2007.11.003.
Proper ovarian development requires the cell type-specific transcription factor TAF4b, a subunit of the core promoter recognition complex TFIID. We present the 35 A structure of a cell type-specific core promoter recognition complex containing TAF4b and TAF4 (4b/4-IID), which is responsible for directing transcriptional synergy between c-Jun and Sp1 at a TAF4b target promoter. As a first step toward correlating potential structure/function relationships of the prototypic TFIID versus 4b/4-IID, we have compared their 3D structures by electron microscopy and single-particle reconstruction. These studies reveal that TAF4b incorporation into TFIID induces an open conformation at the lobe involved in TFIIA and putative activator interactions. Importantly, this open conformation correlates with differential activator-dependent transcription and promoter recognition by 4b/4-IID. By combining functional and structural analysis, we find that distinct localized structural changes in a megadalton macromolecular assembly can significantly alter its activity and lead to a TAF4b-induced reprogramming of promoter specificity.
正常的卵巢发育需要细胞类型特异性转录因子TAF4b，它是核心启动子识别复合物TFIID的一个亚基。我们展示了包含TAF4b和TAF4的细胞类型特异性核心启动子识别复合物（4b/4-IID）的35 Å结构，该复合物负责在TAF4b靶启动子处指导c-Jun和Sp1之间的转录协同作用。作为将原型TFIID与4b/4-IID的潜在结构/功能关系相关联的第一步，我们通过电子显微镜和单颗粒重建比较了它们的三维结构。这些研究表明，TAF4b掺入TFIID会在涉及TFIIA和假定激活剂相互作用的叶处诱导开放构象。重要的是，这种开放构象与4b/4-IID依赖于激活剂的差异转录和启动子识别相关。通过结合功能和结构分析，我们发现兆道尔顿大分子组装体中不同的局部结构变化可显著改变其活性，并导致TAF4b诱导的启动子特异性重编程。
