Figure 2

a) Mediator plays key roles in the assembly of the Pre-initiation Complex (PIC). Mediator helps recruit pol II and other PIC factors to the promoter¹⁹¹. At this stage, the pol II CTD is not highly phosphorylated. During transcription initiation, the pol II CTD becomes highly phosphorylated by TFIIH⁸⁰, and the pol II enzyme begins to transcribe the gene. At some genes, pol II may pause after transcribing about 60 nucleotides⁹⁵; whether this “paused pol II” remains associated with Mediator is not known. b) The CDK8 module may associate with Mediator after pol II-Mediator contacts are broken, and this may regulate pol II elongation or release from a paused state at some genes. CDK8-Mediator may regulate the recruitment or activity of the super elongation complex (SEC) to promote pol II pause release and elongation^27,28. c) Because CDK8-Mediator cannot interact with pol II, re-initiation of transcription requires release of the CDK8 module. A scaffold PIC complex, which may be stabilized by a transcription factor, could facilitate rapid re-initiation¹¹⁰.