Fig. 1. The yeast mediator model of activator-dependent transcription. Shown is a hypothetical promoter containing a canonical TATA box and interacting with the TFIID complex. Additional TFIID contacts are made with the initiator element (at the start site) and downstream of the start site. The arrow within the TFIID complex represents the start site of transcription. The three activators (GCN4, VP16 and GAL4) are shown binding to their DNA sites and recruiting yeast mediator to the promoter via a physical interaction with a mediator module (indicated by the overlap between the activator and the respective mediator module) (Koh et al., 1998; Lee et al., 1999b). Additional overlap among the three yeast mediator modules represents physical interactions between the three modules. Lastly, overlap/physical interactions between the MED9/MED10 and SRB4 modules and RNA polymerase II are illustrated (Kang et al., 2001). The HEAD, MIDDLE and TAIL domains are indicated and are based on recent structural data (Asturias et al., 1999; Davis et al., 2002; Dotson et al., 2000b). Note that the negative regulation of TFIIH CAK (cyclin H/cdk7) by the SRB10/SRB11 (cyclin-C-CDK8) is specific to human and has not been observed in yeast (Akoulitchev et al., 2000).