title: Reconstruction of gene association network reveals a transmembrane protein required for adipogenesis and targeted by PPARγ.
abstract: We have developed a method for reconstructing gene association networks and have applied this method to gene profiles from 3T3-L1 cells. Priorization of the candidate genes pinpointed a transcript annotated as APMAP (adipocyte plasma membrane-associated protein). Functional studies showed that APMAP is upregulated in murine and human adipogenic cell models as well as in a genetic mouse model of obesity. Silencing APMAP in 3T3-L1 cells strongly impaired the differentiation into adipocytes. Moreover, APMAP expression was strongly induced by the PPARγ ligand rosiglitazone in adipocytes in vitro and in vivo in adipose tissue. Using ChIP-qPCR and luciferase reporter assays, we show a functional PPARγ binding site. In addition, we provide evidence that the extracellular C-terminal domain of APMAP is required for the function of APMAP in adipocyte differentiation. Finally, we demonstrate that APMAP translocates from the endoplasmatic reticulum to the plasma membrane during adipocyte differentiation.
authors.affiliation: Institute for Genomics and Bioinformatics, Graz University of Technology, Petersgasse 14, 8010 Graz, Austria. juliane.bogner-strauss@tugraz.at
authors.forename: Juliane G
authors.initials: JG
authors.lastname: Bogner-Strauss
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokesch
authors.forename: Fatima
authors.initials: F
authors.lastname: Sanchez-Cabo
authors.forename: Dietmar
authors.initials: D
authors.lastname: Rieder
authors.forename: Hubert
authors.initials: H
authors.lastname: Hackl
authors.forename: Kalina
authors.initials: K
authors.lastname: Duszka
authors.forename: Anne
authors.initials: A
authors.lastname: Krogsdam
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Camillo
authors.forename: Evelyn
authors.initials: E
authors.lastname: Walenta
authors.forename: Ariane
authors.initials: A
authors.lastname: Klatzer
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pinent
authors.forename: Wing-Cheong
authors.initials: WC
authors.lastname: Wong
authors.forename: Frank
authors.initials: F
authors.lastname: Eisenhaber
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics*; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C439388:APMAP protein, mouse; D008562:Membrane Glycoproteins; D047495:PPAR gamma; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins