title: Identification of the transcription factor ZEB1 as a central component of the adipogenic gene regulatory network.
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.
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Carine
authors.initials: C
authors.lastname: Gubelmann
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Petra C
authors.initials: PC
authors.lastname: Schwalie
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Raghav
authors.affiliation: Institute of Food Nutrition and Health, Eidgenössische Technische Hochschule Zürich, Schwerzenbach, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Röder
authors.affiliation: Institute of Food Nutrition and Health, Eidgenössische Technische Hochschule Zürich, Schwerzenbach, Switzerland.
authors.forename: Tenagne
authors.initials: T
authors.lastname: Delessa
authors.affiliation: Institute of Food Nutrition and Health, Eidgenössische Technische Hochschule Zürich, Schwerzenbach, Switzerland.
authors.forename: Elke
authors.initials: E
authors.lastname: Kiehlmann
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Sebastian M
authors.identifier: http://orcid.org/0000-0003-3042-9521
authors.initials: SM
authors.lastname: Waszak
authors.affiliation: Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Corsinotti
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Gilles
authors.initials: G
authors.lastname: Udin
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Holcombe
authors.affiliation: Ärztlicher Leiter Endokrinologie, Diabetologie und Klinische Ernährung Kantonsspital Olten, Olten, Switzerland.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Rudofsky
authors.affiliation: Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
authors.affiliation: Institute of Food Nutrition and Health, Eidgenössische Technische Hochschule Zürich, Schwerzenbach, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Wolfrum
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015870:Gene Expression; D053263:Gene Regulatory Networks / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D047495:PPAR gamma; D014157:Transcription Factors; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: adipogenesis; developmental biology; evolutionary biology; gene regulatory networks; genomics; human; mesenchymal stem cells; mouse; stem cells; transcription factor screen; zeb1