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Curr Opin Cell Biol. 2012 Jun;24(3):305-13. doi: 10.1016/ Epub 2012 Feb 15.

A structural perspective on Mediator function.

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Gene Center and Department of Biochemistry, Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität München, Feodor-Lynen-Straße 25, 81377 Munich, Germany.


Gene transcription by RNA polymerase II requires the multiprotein coactivator complex Mediator. Mediator was identified two decades ago, but its molecular mechanisms remain poorly understood, because structural studies are hampered by its large size, modularity, and flexibility. Here we collect all available structural data on Mediator and discuss their functional implications. Progress was made in understanding the interactions of Mediator with gene-specific transcriptional regulators and the general transcription machinery. However, around 80% of the Mediator structure remains unknown and details on the Mediator-Pol II interface are lacking. In the future, an integrated structural biology approach may unravel the functional architecture of Mediator-regulated promoter assemblies and holds the promise of understanding a key mechanism of gene regulation.

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