Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos

  1. Shai R Joseph
  2. Máté Pálfy
  3. Lennart Hilbert
  4. Mukesh Kumar
  5. Jens Karschau
  6. Vasily Zaburdaev
  7. Andrej Shevchenko
  8. Nadine L Vastenhouw  Is a corresponding author
  1. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  2. Max Planck Institute for the Physics of Complex Systems, Germany
  3. Center for Systems Biology Dresden, Germany

Abstract

Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.

Article and author information

Author details

  1. Shai R Joseph

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Máté Pálfy

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Lennart Hilbert

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4478-5607
  4. Mukesh Kumar

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Jens Karschau

    Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Vasily Zaburdaev

    Center for Systems Biology Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Andrej Shevchenko

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Nadine L Vastenhouw

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    For correspondence
    vastenhouw@mpi-cbg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8782-9775

Funding

Human Frontier Science Program (CDA00060/2012)

  • Nadine L Vastenhouw

Deutsche Forschungsgemeinschaft

  • Shai R Joseph
  • Mukesh Kumar

Max-Planck-Gesellschaft

  • Vasily Zaburdaev
  • Andrej Shevchenko
  • Nadine L Vastenhouw

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Joseph et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 7,747
    views
  • 1,387
    downloads
  • 130
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Shai R Joseph
  2. Máté Pálfy
  3. Lennart Hilbert
  4. Mukesh Kumar
  5. Jens Karschau
  6. Vasily Zaburdaev
  7. Andrej Shevchenko
  8. Nadine L Vastenhouw
(2017)
Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos
eLife 6:e23326.
https://doi.org/10.7554/eLife.23326

Share this article

https://doi.org/10.7554/eLife.23326

Further reading

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Ruben Sebastian-Perez, Shoma Nakagawa ... Maria Pia Cosma
    Research Article

    Chromocenters are established after the 2-cell (2C) stage during mouse embryonic development, but the factors that mediate chromocenter formation remain largely unknown. To identify regulators of 2C heterochromatin establishment in mice, we generated an inducible system to convert embryonic stem cells (ESCs) to 2C-like cells. This conversion is marked by a global reorganization and dispersion of H3K9me3-heterochromatin foci, which are then reversibly formed upon re-entry into pluripotency. By profiling the chromatin-bound proteome (chromatome) through genome capture of ESCs transitioning to 2C-like cells, we uncover chromatin regulators involved in de novo heterochromatin formation. We identified TOPBP1 and investigated its binding partner SMARCAD1. SMARCAD1 and TOPBP1 associate with H3K9me3-heterochromatin in ESCs. Interestingly, the nuclear localization of SMARCAD1 is lost in 2C-like cells. SMARCAD1 or TOPBP1 depletion in mouse embryos leads to developmental arrest, reduction of H3K9me3, and remodeling of heterochromatin foci. Collectively, our findings contribute to comprehending the maintenance of chromocenters during early development.

    1. Developmental Biology
    Yunfei Mu, Shijia Hu ... Hongjun Shi
    Research Article

    Notch signaling has been identified as a key regulatory pathway in patterning the endocardium through activation of endothelial-to-mesenchymal transition (EMT) in the atrioventricular canal (AVC) and proximal outflow tract (OFT) region. However, the precise mechanism underlying Notch activation remains elusive. By transiently blocking the heartbeat of E9.5 mouse embryos, we found that Notch activation in the arterial endothelium was dependent on its ligand Dll4, whereas the reduced expression of Dll4 in the endocardium led to a ligand-depleted field, enabling Notch to be specifically activated in AVC and OFT by regional increased shear stress. The strong shear stress altered the membrane lipid microdomain structure of endocardial cells, which activated mTORC2 and PKC and promoted Notch1 cleavage even in the absence of strong ligand stimulation. These findings highlight the role of mechanical forces as a primary cue for endocardial patterning and provide insights into the mechanisms underlying congenital heart diseases of endocardial origin.