Different upstream transcriptional activators have distinct coactivator requirements.

Activated transcription by RNA polymerase II (Pol II) requires coactivators, one of which is the SRB/mediator. Whereas Srb4, an essential subunit of the SRB/mediator, is broadly required for Pol II transcription in yeast, we have shown that it is dispensable for the transcriptional activation of some genes. Here, we show that transcriptional activation by different natural activators, and by artificial recruitment of various transcription factors, have very different degrees of Srb4 independence. These data, and the analysis of an rgr1 mutant, point to an Rgr1 subcomplex of the SRB/mediator as the mechanistic route of activation by Srb4-independent activators in vivo.