Mediator is broadly recruited to gene promoters via a Tail-independent mechanism

Abstract

Mediator (MED) is a conserved factor with important roles in both basal and activated transcription. It is believed that MED plays a direct role in transcriptional regulation at most genes by functionally bridging enhancers and promoters. 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. We find that MED Tail and activator-mediated MED recruitment regulate only a small subset of genes. At most genes, MED bypasses the UAS and is directly recruited to promoters to facilitate transcription initiation. Our results define three classes of genes that differ in PIC assembly pathways and the requirements for MED Tail, SAGA, TFIID and BET factors Bdf1/2. We also find that the depletion of the MED middle module subunit Med7 mimics inactivation of Tail, suggesting a functional link. Our combined results have broad implications for the roles of MED, other coactivators, and mechanisms of transcriptional regulation at different gene classes.