Not only is Mediator dynamic in its structure/conformation, it is also dynamic in its subunit composition.  Our lab and others have observed that various Mediator subunits can exchange with the core complex.  For example, a 600 kDa CDK8 module 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.  Significantly, such subunit exchange within Mediator alters its activity.  For example, loss of MED1 and MED26 prevents Mediator-dependent activation at nuclear receptor (NR) target genes, given that MED1 is a primary target for NR binding.  Thus, subunit loss can bestow promoter-selective functionality to Mediator.  Additionally, Mediator-CDK8 module interaction blocks Mediator-pol II binding, which regulates transcription initiation or re-initiation events at the promoter.  We have also uncovered a role for CDK8-Mediator in the regulation of transcription elongation, as has the Espinosa lab.  Ongoing projects will continue to define how subunit exchange affects the biological function of Mediator, including whether additional cofactors associate with or dissociate from Mediator, and how this controls Mediator function.

Lab publications related to Mediator subunit exchange:
Meyer, KD; Donner, AJ; Knuesel, MT; York, AG; Espinosa, JM; Taatjes, DJ. Cooperative activity of CDK8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3. EMBO J 2008, 27: 1447-1457.
Knuesel, MT; Meyer, KD; Bernecky, C; Taatjes, DJ. The human CDK8 subcomplex is a molecular switch that controls Mediator co-activator function. Genes & Dev 2009, 23: 439-451.
Knuesel, MT; Meyer, KD; Donner, AJ; Espinosa, JM; Taatjes, DJ. The human CDK8 subcomplex is a histone kinase that requires MED12 for activity and can function independently of Mediator. Mol Cell Biol 2009, 29: 650-661.
Donner, AJ; Ebmeier, CC; Taatjes, DJ; Espinosa, JM. CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nature SMB 2010, 17: 194-201.
Ebmeier, CC; Taatjes, DJ. Activator-Mediator binding regulates Mediator-cofactor interactions. PNAS 2010, 107: 11283-11288.