Mediator facilitates transcription initiation at most promoters via a Tail-independent mechanism [ChEC-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）是一类保守因子，在基础转录与激活态转录中发挥关键调控作用。本研究通过快速敲降酵母中介体（MED）的激活因子结合结构域Tail，并监测新生转录的变化，探究了MED在全基因组层面的功能。令人意外的是，快速Tail结构域敲降仅能下调一小部分基因的转录水平。在多数此类Tail依赖型基因中，未受干扰的条件下，MED可同时结合于上游激活序列（Upstream Activating Sequences，UAS）与启动子区域；与之相对，在多数非Tail依赖型基因中，MED主要富集于启动子区域，而不结合UAS。上述结果表明，MED Tail结构域与激活因子介导的MED招募仅对一小部分基因的转录具有调控功能。进一步而言，本研究定义了三类基因，它们在转录预起始复合物（Preinitiation Complex，PIC）组装通路，以及对MED Tail、SAGA、转录因子IID（Transcription Factor II D，TFIID）和溴域和额外末端结构域（Bromodomain and Extra-Terminal，BET）家族因子Bdf1/2的需求上存在显著差异。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，均具有广泛的启示意义。