The general transcription factors and Mediator assemble at a core promoter to form a pre-initiation complex (PIC). Upon PIC formation, Kin28-dependent phosphorylation of Pol II CTD inhibits the interaction between Pol II and Mediator, leading to a rapid dissociation of Mediator from the PIC, facilitating Pol II escape from the PIC for productive elongation. Although it is formally possible that Mediator dissociation and Pol II escape from the PIC occur simultaneously or in the reverse order, we disfavor this possibility as CTD phosphorylation destabilizes the direct Mediator-Pol II interaction in vitro, and there is no evidence in vivo for direct stable Mediator-PIC association in the absence of Pol II. After Pol II promoter escape, a “post-escape” transcription initiation complex, which is relatively stable (minute time scale), remains bound at the core promoter such that transcription re-initiation can occur upon reloading of Mediator and Pol II.