Mediator complex interaction partners organize the transcriptional network that defines neural stem cells

Marti Quevedo, Lize Meert, Mike R. Dekker, Dick H. W. Dekkers, Johannes H. Brandsma, Debbie L. C. Berg, Zeliha Ozgür, Wilfred F. J. van IJcken, Jeroen Demmers, Maarten Fornerod and Raymond A. Poot ()
Additional contact information
Marti Quevedo: Erasmus MC
Lize Meert: Erasmus MC
Mike R. Dekker: Erasmus MC
Dick H. W. Dekkers: Erasmus MC
Johannes H. Brandsma: Erasmus MC
Debbie L. C. Berg: Erasmus MC
Zeliha Ozgür: Erasmus MC
Wilfred F. J. van IJcken: Erasmus MC
Jeroen Demmers: Erasmus MC
Maarten Fornerod: Erasmus MC
Raymond A. Poot: Erasmus MC

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract The Mediator complex regulates transcription by connecting enhancers to promoters. High Mediator binding density defines super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of Mediator may explain its role in these processes but have not been identified comprehensively. Here, we purify Mediator from neural stem cells (NSCs) and identify 75 protein-protein interaction partners. We identify super enhancers in NSCs and show that Mediator-interacting chromatin modifiers colocalize with Mediator at enhancers and super enhancers. Transcription factor families with high affinity for Mediator dominate enhancers and super enhancers and can explain genome-wide Mediator localization. We identify E-box transcription factor Tcf4 as a key regulator of NSCs. Tcf4 interacts with Mediator, colocalizes with Mediator at super enhancers and regulates neurogenic transcription factor genes with super enhancers and broad H3K4me3 domains. Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity.

Date: 2019
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DOI: 10.1038/s41467-019-10502-8

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