The SAGA coactivator complex is essential for eukaryotic transcription and comprises four distinct modules, one of which contains the ubiquitin hydrolase USP22. In yeast, the USP22 ortholog deubiquitylates H2B, resulting in Pol II Ser2 phosphorylation and subsequent transcriptional elongation. In contrast to this H2B-associated role in transcription, we report here that human USP22 contributes to the early stages of stimulus-responsive transcription, where USP22 is required for pre-initiation complex (PIC) stability. Specifically, USP22 maintains long-range enhancer–promoter contacts and controls loading of Mediator tail and general transcription factors (GTFs) onto promoters, with Mediator core recruitment being USP22-independent. In addition, we identify Mediator tail subunits MED16 and MED24 and the Pol II subunit RBP1 as potential non-histone substrates of USP22. Overall, these findings define a role for human SAGA within the earliest steps of transcription.

中文翻译：

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SAGA 复合物通过其去泛素化酶模块亚基 USP22 调节转录的早期步骤

SAGA 共激活因子复合物对真核转录至关重要，它包含四个不同的模块，其中一个包含泛素水解酶 USP22。在酵母中，USP22 直系同源物去泛素化 H2B，导致 Pol II Ser2 磷酸化和随后的转录延伸。与这种 H2B 在转录中的相关作用相反，我们在此报告人类 USP22 有助于刺激响应转录的早期阶段，其中 USP22 是启动前复合物 (PIC) 稳定性所必需的。具体而言，USP22 维持长程增强子-启动子接触并控制介体尾部和一般转录因子 (GTF) 加载到启动子上，而介体核心募集不依赖于 USP22。此外，我们将介体尾部亚基 MED16 和 MED24 以及 Pol II 亚基 RBP1 鉴定为 USP22 的潜在非组蛋白底物。总的来说，这些发现定义了人类 SAGA 在转录最早步骤中的作用。