Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Mailstop A1-162, Seattle, WA 98109, USA.
Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Mailstop A1-162, Seattle, WA 98109, USA.
Mol Cell. 2022 Nov 3;82(21):4033-4048.e7. doi: 10.1016/j.molcel.2022.09.016. Epub 2022 Oct 7.
Mediator (MED) is a conserved factor with important roles in basal and activated transcription. Here, we investigate the genome-wide roles of yeast MED by rapid depletion of its activator-binding domain (Tail) and monitoring changes in nascent transcription. Rapid Tail depletion surprisingly reduces transcription from only a small subset of genes. At most of these Tail-dependent genes, in unperturbed conditions, MED is detected at both the UASs and promoters. In contrast, at most Tail-independent genes, we find MED primarily at promoters but not at the UASs. These results suggest that MED Tail and activator-mediated MED recruitment regulates only a small subset of genes. Furthermore, we define three classes of genes that differ in PIC assembly pathways and the requirements for MED Tail, SAGA, TFIID, and BET factors Bdf1/2. Our combined results have broad implications for the roles of MED, other coactivators, and mechanisms of transcriptional regulation at different gene classes.
介体（MED）是一种保守因子，在基础转录和激活转录中具有重要作用。在这里，我们通过快速耗尽其激活剂结合结构域（尾部）并监测新生转录的变化来研究酵母 MED 的全基因组作用。令人惊讶的是，快速尾部耗竭仅减少了一小部分基因的转录。在大多数依赖尾部的基因中，在未受干扰的条件下，在 UAS 和启动子上都检测到 MED。相比之下，在大多数不依赖尾部的基因中，我们发现 MED 主要位于启动子上，而不是 UAS 上。这些结果表明，MED 尾部和激活剂介导的 MED 募集仅调节一小部分基因。此外，我们定义了三类基因，它们在 PIC 组装途径以及 MED 尾部、SAGA、TFIID 和 BET 因子 Bdf1/2 的需求方面存在差异。我们的综合结果对不同基因类别中 MED、其他共激活因子以及转录调控机制的作用具有广泛的意义。
