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JMJD3 intrinsically disordered region links the 3D-genome structure to TGFβ-dependent transcription activation

Author

Listed:
  • Marta Vicioso-Mantis

    (Consejo Superior de Investigaciones Científicas (CSIC))

  • Raquel Fueyo

    (Consejo Superior de Investigaciones Científicas (CSIC)
    Stanford University)

  • Claudia Navarro

    (Consejo Superior de Investigaciones Científicas (CSIC))

  • Sara Cruz-Molina

    (University of Cologne)

  • Wilfred F. J. Ijcken

    (Erasmus University Medical Center Rotterdam)

  • Elena Rebollo

    (Consejo Superior de Investigaciones Científicas (CSIC))

  • Álvaro Rada-Iglesias

    (University of Cologne
    CSIC/University of Cantabria)

  • Marian A. Martínez-Balbás

    (Consejo Superior de Investigaciones Científicas (CSIC))

Abstract

Enhancers are key regulatory elements that govern gene expression programs in response to developmental signals. However, how multiple enhancers arrange in the 3D-space to control the activation of a specific promoter remains unclear. To address this question, we exploited our previously characterized TGFβ-response model, the neural stem cells, focusing on a ~374 kb locus where enhancers abound. Our 4C-seq experiments reveal that the TGFβ pathway drives the assembly of an enhancer-cluster and precise gene activation. We discover that the TGFβ pathway coactivator JMJD3 is essential to maintain these structures. Using live-cell imaging techniques, we demonstrate that an intrinsically disordered region contained in JMJD3 is involved in the formation of phase-separated biomolecular condensates, which are found in the enhancer-cluster. Overall, in this work we uncover novel functions for the coactivator JMJD3, and we shed light on the relationships between the 3D-conformation of the chromatin and the TGFβ-driven response during mammalian neurogenesis.

Suggested Citation

  • Marta Vicioso-Mantis & Raquel Fueyo & Claudia Navarro & Sara Cruz-Molina & Wilfred F. J. Ijcken & Elena Rebollo & Álvaro Rada-Iglesias & Marian A. Martínez-Balbás, 2022. "JMJD3 intrinsically disordered region links the 3D-genome structure to TGFβ-dependent transcription activation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30614-y
    DOI: 10.1038/s41467-022-30614-y
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