Coactivator complexes regulate chromatin accessibility and transcription. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved coactivator complex. The core module scaffolds the entire SAGA complex and adopts a histone octamer-like structure, which consists of six histone-fold domain (HFD)-containing proteins forming three histone-fold (HF) pairs, to which the double HFD-containing SUPT3H adds one HF pair. Spt3, the yeast ortholog of SUPT3H, interacts genetically and biochemically with the TATA binding protein (TBP) and contributes to global RNA polymerase II (Pol II) transcription. Here we demonstrate that (i) SAGA purified from human U2OS or mouse embryonic stem cells (mESC) can assemble without SUPT3H, (ii) SUPT3H is not essential for mESC survival, but required for their growth and self-renewal, and (iii) the loss of SUPT3H from mammalian cells affects the transcription of only a specific subset of genes. Accordingly, in the absence of SUPT3H no major change in TBP accumulation at gene promoters was observed. Thus, SUPT3H is not required for the assembly of SAGA, TBP recruitment, or overall Pol II transcription, but plays a role in mESC growth and self-renewal. Our data further suggest that yeast and mammalian SAGA complexes contribute to transcription regulation by distinct mechanisms.

中文翻译：

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无 SUPT3H 的 SAGA 共激活剂可以组装和发挥作用，而不会显着干扰哺乳动物细胞中的 RNA 聚合酶 II 转录

共激活复合物调节染色质的可及性和转录。SAGA (Spt-Ada-Gcn5 Acetyltransferase) 是一种进化保守的共激活复合物。核心模块支撑整个 SAGA 复合物并采用类组蛋白八聚体结构，该结构由六个含组蛋白折叠结构域 (HFD) 的蛋白质组成，形成三个组蛋白折叠 (HF) 对，含双 HFD 的 SUPT3H 添加到其中一对HF。Spt3 是 SUPT3H 的酵母直系同源物，与 TATA 结合蛋白 (TBP) 发生遗传和生化相互作用，并有助于全球 RNA 聚合酶 II (Pol II) 转录。在这里，我们证明 (i) 从人类 U2OS 或小鼠胚胎干细胞 (mESC) 中纯化的 SAGA 可以在没有 SUPT3H 的情况下组装，(ii) SUPT3H 对 mESC 存活不是必需的，但它们的生长和自我更新是必需的，(iii) 哺乳动物细胞中 SUPT3H 的缺失仅影响特定基因子集的转录。因此，在没有 SUPT3H 的情况下，没有观察到基因启动子处 TBP 积累的重大变化。因此，SAGA、TBP 募集或整体 Pol II 转录不需要 SUPT3H，但在 mESC 生长和自我更新中发挥作用。我们的数据进一步表明酵母和哺乳动物 SAGA 复合物通过不同的机制促进转录调控。