title: An Evi1-C/EBPβ complex controls peroxisome proliferator-activated receptor γ2 gene expression to initiate white fat cell differentiation.
abstract: Fibroblastic preadipocyte cells are recruited to differentiate into new adipocytes during the formation and hyperplastic growth of white adipose tissue. Peroxisome proliferator-activated receptor γ (PPARγ), the master regulator of adipogenesis, is expressed at low levels in preadipocytes, and its levels increase dramatically and rapidly during the differentiation process. However, the mechanisms controlling the dynamic and selective expression of PPARγ in the adipocyte lineage remain largely unknown. We show here that the zinc finger protein Evi1 increases in preadipocytes at the onset of differentiation prior to increases in PPARγ levels. Evi1 expression converts nonadipogenic cells into adipocytes via an increase in the predifferentiation levels of PPARγ2, the adipose-selective isoform of PPARγ. Conversely, loss of Evi1 in preadipocytes blocks the induction of PPARγ2 and suppresses adipocyte differentiation. Evi1 binds with C/EBPβ to regulatory sites in the Pparγ locus at early stages of adipocyte differentiation, coincident with the induction of Pparγ2 expression. These results indicate that Evi1 is a key regulator of adipogenic competency.
authors.affiliation: Institute for Diabetes, Obesity and Metabolism, Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Ishibashi
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Firtina
authors.forename: Sona
authors.initials: S
authors.lastname: Rajakumari
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Wood
authors.forename: Heather M
authors.initials: HM
authors.lastname: Conroe
authors.forename: David J
authors.initials: DJ
authors.lastname: Steger
authors.forename: Patrick
authors.initials: P
authors.lastname: Seale
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011519:Proto-Oncogenes / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D047495:PPAR gamma; D014157:Transcription Factors