1. Developmental Biology
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Identification of the transcription factor ZEB1 as a central component of the adipogenic gene regulatory network

  1. Carine Gubelmann
  2. Petra C Schwalie
  3. Sunil K Raghav
  4. Eva Röder
  5. Tenagne Delessa
  6. Elke Kiehlmann
  7. Sebastian M Waszak
  8. Andrea Corsinotti
  9. Gilles Udin
  10. Wiebke Holcombe
  11. Gottfried Rudofsky
  12. Didier Trono
  13. Christian Wolfrum
  14. Bart Deplancke  Is a corresponding author
  1. Ecole Polytechnique Fédérale de Lausanne, Switzerland
  2. Institute of Life Sciences, India
  3. ETH Zürich, Switzerland
  4. European Molecular Biology Laboratory, Germany
  5. University of Edinburgh, Scotland
  6. Diabetologie und Klinische Ernährung Kantonsspital Olten, Switzerland
Research Article
  • Cited 42
  • Views 6,171
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Cite this article as: eLife 2014;3:e03346 doi: 10.7554/eLife.03346

Abstract

Adipose tissue is a key determinant of whole body metabolism and energy homeostasis. Unraveling the regulatory mechanisms underlying adipogenesis is therefore highly relevant from a biomedical perspective. Our current understanding of fat cell differentiation is centered on the transcriptional cascades driven by the C/EBP protein family and the master regulator PPARγ. To elucidate further components of the adipogenic gene regulatory network, we performed a large-scale transcription factor (TF) screen overexpressing 734 TFs in mouse pre-adipocytes and probed their effect on differentiation. We identified 23 novel pro-adipogenic TFs and characterized the top ranking TF, ZEB1, as being essential for adipogenesis both in vitro and in vivo. Moreover, its expression levels correlate with fat cell differentiation potential in humans. Genomic profiling further revealed that this TF directly targets and controls the expression of most early and late adipogenic regulators, identifying ZEB1 as a central transcriptional component of fat cell differentiation.

Article and author information

Author details

  1. Carine Gubelmann

    Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Petra C Schwalie

    Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Sunil K Raghav

    Institute of Life Sciences, Bhubaneswar, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Eva Röder

    ETH Zürich, Schwerzenbach, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Tenagne Delessa

    ETH Zürich, Schwerzenbach, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Elke Kiehlmann

    ETH Zürich, Schwerzenbach, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Sebastian M Waszak

    European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Andrea Corsinotti

    University of Edinburgh, Edinburgh, Scotland
    Competing interests
    The authors declare that no competing interests exist.
  9. Gilles Udin

    Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  10. Wiebke Holcombe

    Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  11. Gottfried Rudofsky

    Diabetologie und Klinische Ernährung Kantonsspital Olten, Olten, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  12. Didier Trono

    Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  13. Christian Wolfrum

    ETH Zürich, Schwerzenbach, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  14. Bart Deplancke

    Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    For correspondence
    bart.deplancke@epfl.ch
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experiments were conducted in strict accordance with Swiss law and all experiments were approved by the ethics commission of the state veterinary office (60/2012, 43/2011).

Human subjects: The work on obese subjects was approved by the ethics committee at the University Hospital of Heidelberg and is conforming to the ethical guidelines of the 2000 Helsinki declaration. All participants provided witnessed written informed consent prior entering the study (S-365/2007). The trial was registered as NCT00773565.

Reviewing Editor

  1. Peter Tontonoz, University of California, Los Angeles, United States

Publication history

  1. Received: May 13, 2014
  2. Accepted: August 24, 2014
  3. Accepted Manuscript published: August 27, 2014 (version 1)
  4. Version of Record published: September 19, 2014 (version 2)

Copyright

© 2014, Gubelmann 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.

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