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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Raymond A. P, 2019. "Mediator complex interaction partners organize the transcriptional network that defines neural stem cells," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10502-8
    DOI: 10.1038/s41467-019-10502-8
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    Cited by:

    1. Juan Manuel Valverde & Geronimo Dubra & Michael Phillips & Austin Haider & Carlos Elena-Real & Aurélie Fournet & Emile Alghoul & Dhanvantri Chahar & Nuria Andrés-Sanchez & Matteo Paloni & Pau Bernadó , 2023. "A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    2. Feng Bai & Peng Shu & Heng Deng & Yi Wu & Yao Chen & Mengbo Wu & Tao Ma & Yang Zhang & Julien Pirrello & Zhengguo Li & Yiguo Hong & Mondher Bouzayen & Mingchun Liu, 2024. "A distal enhancer guides the negative selection of toxic glycoalkaloids during tomato domestication," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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