Not only is Mediator dynamic in its structure/conformation, it is also dynamic in its subunit composition. Us and others have observed that various Mediator subunits can "exchange" from the complex. For example, a "cdk8 subcomplex" consisting of 4 polypeptides (Med12, Med13, cdk8, cyclin C) can variably associate with Mediator. In addition, the Mediator subunits Med1 and Med26 can dissociate from the complex, leaving a "derivative" complex called Mediator2. Significantly, when this "subunit exchange" occurs, the activity of the Mediator complex changes. The cdk8 subcomplex, for example, primarily works to repress Mediator co-activator function, whereas the loss of Med1/Med26 causes Mediator to adopt promoter-selective functions. Our lab is studying how subunit exchange affects the biochemical function of Mediator. We are also working to identify whether additional subcomplexes associate with or dissociate from Mediator, and what effect this may have on regulating Mediator function.