The Mediator complex: a central integrator of transcription

The RNA polymerase II (Pol II) enzyme transcribes all protein-coding and most non-coding RNA genes and is globally regulated by Mediator — a large, conformationally flexible protein complex with a variable subunit composition (for example, a four-subunit cyclin-dependent kinase 8 module can reversibly associate with it). These biochemical characteristics are fundamentally important for Mediator's ability to control various processes that are important for transcription, including the organization of chromatin architecture and the regulation of Pol II pre-initiation, initiation, re-initiation, pausing and elongation. Although Mediator exists in all eukaryotes, a variety of Mediator functions seem to be specific to metazoans, which is indicative of more diverse regulatory requirements.

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Acknowledgements

The authors thank A. Shilatifard and the reviewers for comments on the manuscript. They apologize that they could not discuss other important and relevant research owing to space and citation limits. D.J.T.'s laboratory is supported by the US National Science Foundation (MCB-1244175) and the US National Cancer Institute (CA175849; CA1707041; CA175448). B.L.A. has been supported in part by the US National Institutes of Health (T32 GM08759).