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Nat Commun. 2019 Jun 17;10(1):2669. doi: 10.1038/s41467-019-10502-8.

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

Author information

1
Department of Cell Biology, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, Netherlands.
2
Center for Proteomics, Erasmus MC, 3015 CN, Rotterdam, Netherlands.
3
Center for Biomics, Erasmus MC, 3015 CN, Rotterdam, Netherlands.
4
Department of Cell Biology, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, Netherlands. r.poot@erasmusmc.nl.

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.

PMID:
31209209
PMCID:
PMC6573065
DOI:
10.1038/s41467-019-10502-8
[Indexed for MEDLINE]
Free PMC Article

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