Figure 1

This schematic illustrates that as the structure of Mediator changes, its ability to interact with other regulatory proteins may also change. Such structural transitions could enable the same Mediator complex to adopt distinct functions at the appropriate stages of transcription (for example, initiation vs. elongation). Also, the model allows for some cofactors to bind Mediator in several different structural states. a) Upon binding a transcription factor (TF), Mediator undergoes structural changes that facilitate interactions with additional transcription regulators⁴³. Structural changes associated with TF-Mediator binding also appear to promote stable association with pol II¹⁹⁷, and correlate with activation of transcription⁴¹. b) Binding of pol II triggers distinct structural changes throughout Mediator^58,59; these might be important for functional interactions between Mediator and factors that promote pol II initiation and/or elongation, such as TFIIS, TFIIF, or POLR2M^{72,76,104,105}. c) CDK8 module–Mediator binding also induces structural changes in Mediator that prevent pol II binding^18,198; further, CDK8-Mediator associates with elongation factors such as the SEC^27,43, which may regulate the timing of SEC recruitment at some genes.