Mediator (coactivator)

Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. It was discovered in the lab of Roger D. Kornberg, winner of the 2006 Nobel Prize in Chemistry. Mediator complexes interact with transcription factors and RNA polymerase II. The main (but not exclusive) function of mediator complexes is to transmit signals from the transcription factors to the polymerase.

Mediator complexes are variable at the evolutionary, compositional and conformational levels. The first image shows only one "snapshot" of what a particular mediator complex might be composed of, but it certainly does not accurately depict the conformation of the complex in vivo. During evolution, mediator has become more complex. The yeast Saccharomyces cerevisiae (a simple eukaryote) is thought to have up to 21 subunits in the core mediator (exclusive of the CDK module), while mammals have up to 26.

Individual subunits can be absent or replaced by other subunits under different conditions. Also, there are many intrinsically disordered regions in mediator proteins, which may contribute to the conformational flexibility seen both with and without other bound proteins or protein complexes. A more realistic model of a mediator complex without the CDK module is shown in the second figure.

The mediator complex is required for the successful transcription by RNA polymerase II. Mediator has been shown to make contacts with the polymerase in the transcription preinitiation complex. A recent model showing the association of the polymerase

with mediator in the absence of DNA is shown in the figure to the left. In addition to RNA polymerase II, mediator must also associate with transcription factors and DNA. A model of such interactions is shown in the figure to the right. Note that the different morphologies of mediator do not necessarily mean that one of the models is correct; rather those differences may reflect the flexibility of mediator as it interacts with other molecules.

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