1. Developmental Biology and Stem Cells
  2. Genomics and Evolutionary Biology
Download icon

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
12
Views
4,928
Comments
0
Cite 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

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

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

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

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

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

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

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

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

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

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

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

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

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

    1. Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    For correspondence
    1. 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, Reviewing Editor, 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.

Metrics

  • 4,928
    Page views
  • 467
    Downloads
  • 12
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Comments

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)

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

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

Further reading

    1. Computational and Systems Biology
    2. Genomics and Evolutionary Biology
    Aashiq Hussain Kachroo et al.
    Research Article