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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis / genetics*
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Nucleus / metabolism
  • Gene Expression
  • Gene Regulatory Networks / genetics*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Mice, Inbred C3H
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Protein Binding
  • RNA Interference
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc Finger E-box-Binding Homeobox 1


  • CCAAT-Enhancer-Binding Protein-beta
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • PPAR gamma
  • Transcription Factors
  • ZEB1 protein, mouse
  • Zinc Finger E-box-Binding Homeobox 1