Proteomics

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

ABSTRACT: 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 colocalise 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, colocalises 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.

INSTRUMENT(S): LTQ Orbitrap, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Stem Cell

SUBMITTER: Jeroen Demmers  

LAB HEAD: Jeroen Demmers

PROVIDER: PXD013546 | Pride | 2019-05-06

REPOSITORIES: Pride

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

Quevedo Marti M   Meert Lize L   Dekker Mike R MR   Dekkers Dick H W DHW   Brandsma Johannes H JH   van den Berg Debbie L C DLC   Ozgür Zeliha Z   van IJcken Wilfred F J WFJ   Demmers Jeroen J   Fornerod Maarten M   Poot Raymond A RA  

Nature communications 20190617 1

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 mod  ...[more]

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