Mediator facilitates transcription initiation at most promoters via a Tail-independent mechanism [RNA-seq]

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 regulate only a small subset of genes. Further, 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.中介体（Mediator，MED）是一类保守的辅因子，在基础转录与激活转录过程中发挥重要功能。本研究通过快速降解酵母MED的激活因子结合结构域（Tail区域），并监测新生转录的变化，探究了MED在全基因组范围内的调控功能。令人意外的是，快速降解Tail区域仅会使少数基因的转录水平下降。在大多数受Tail调控的基因中，未受外界干扰的状态下，MED可同时结合于上游激活序列（upstream activating sequence, UASs）与启动子区域；与之相反，在大多数不受Tail调控的基因中，MED主要结合于启动子区域，而非上游激活序列。上述结果表明，MED Tail区域与激活因子介导的MED招募仅对少数基因的转录发挥调控作用。进一步而言，本研究定义了三类基因，它们在前起始复合物（preinitiation complex, PIC）组装通路、对MED Tail区域、SAGA复合物、通用转录因子TFIID以及BET家族因子Bdf1/2的需求上存在差异。本研究的综合结果对于理解MED及其他辅激活因子的功能，以及不同基因类别下的转录调控机制具有广泛的启示意义。