Mediator facilitates transcription initiation at most promoters via a Tail-independent mechanism [ChIP-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，在基础转录与激活转录过程中发挥关键作用。本研究通过快速敲降酵母MED的激活因子结合结构域（Tail结构域）并监测新生转录的变化，探究了其在全基因组层面的功能。令人意外的是，快速Tail结构域敲降仅使少量基因的转录水平出现下调。在多数此类Tail依赖型基因的未扰动状态下，可在其上游激活序列（Upstream Activating Sequences，UAS）与启动子区域同时检测到MED；与之相反，在多数Tail非依赖型基因中，MED主要富集于启动子区域，而非上游激活序列（UAS）。上述结果表明，MED Tail结构域与激活因子介导的MED招募仅调控少量基因的转录。进一步而言，本研究界定了三类基因，它们在预起始复合物（Preinitiation Complex，PIC）组装通路、MED Tail结构域需求、SAGA复合物、转录因子IID（Transcription Factor IID，TFIID）以及BET家族因子Bdf1/2的需求方面存在差异。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。