SAGA (Spt–Ada–Gcn5–acetyltransferase) is a 19-subunit complex that stimulates transcription via two chromatin-modifying enzymatic modules and by delivering the TATA box binding protein (TBP) to nucleate the pre-initiation complex on DNA, a pivotal event in the expression of protein-encoding genes¹. Here we present the structure of yeast SAGA with bound TBP. The core of the complex is resolved at 3.5 Å resolution (0.143 Fourier shell correlation). The structure reveals the intricate network of interactions that coordinate the different functional domains of SAGA and resolves an octamer of histone-fold domains at the core of SAGA. This deformed octamer deviates considerably from the symmetrical analogue in the nucleosome and is precisely tuned to establish a peripheral site for TBP, where steric hindrance represses binding of spurious DNA. Complementary biochemical analysis points to a mechanism for TBP delivery and release from SAGA that requires transcription factor IIA and whose efficiency correlates with the affinity of DNA to TBP. We provide the foundations for understanding the specific delivery of TBP to gene promoters and the multiple roles of SAGA in regulating gene expression.

SAGA（Spt-Ada-Gcn5-乙酰转移酶）是一种 19 亚基复合物，通过两个染色质修饰酶模块和通过递送 TATA 盒结合蛋白 (TBP) 使 DNA 上的起始前复合物成核来刺激转录，这是一个关键事件在蛋白质编码基因的表达中¹. 在这里，我们展示了结合 TBP 的酵母 SAGA 的结构。复合物的核心以 3.5 Å 分辨率（0.143 傅里叶壳相关性）解析。该结构揭示了协调 SAGA 不同功能域的复杂相互作用网络，并解析了 SAGA 核心的组蛋白折叠域八聚体。这种变形的八聚体与核小体中的对称类似物有很大的不同，并且经过精确调整以建立 TBP 的外围位点，其中空间位阻抑制假 DNA 的结合。补充生化分析指出了一种从 SAGA 传递和释放 TBP 的机制，该机制需要转录因子 IIA，其效率与 DNA 对 TBP 的亲和力相关。