Format

Send to

Choose Destination
Elife. 2014 Aug 27;3:e03346. doi: 10.7554/eLife.03346.

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

Author information

1
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
2
Institute of Food Nutrition and Health, Eidgenössische Technische Hochschule Zürich, Schwerzenbach, Switzerland.
3
Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
4
Ärztlicher Leiter Endokrinologie, Diabetologie und Klinische Ernährung Kantonsspital Olten, Olten, Switzerland.

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 22 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.

KEYWORDS:

adipogenesis; developmental biology; evolutionary biology; gene regulatory networks; genomics; human; mesenchymal stem cells; mouse; stem cells; transcription factor screen; zeb1

PMID:
25163748
PMCID:
PMC4359378
DOI:
10.7554/eLife.03346
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center