title: Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation.
abstract: BACKGROUND
  Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb) was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate this dual role of pRb in the early and late stages of adipogenesis we used microarrays to perform a comprehensive systems-level analysis of the common transcriptional program of the classic 3T3-L1 preadipocyte cell line, wild-type mouse embryonic fibroblasts (MEFs), and retinoblastoma gene-deficient MEFs (Rb-/- MEFs).
  
  
  RESULTS
  Comparative analysis of the expression profiles of 3T3-L1 cells and wild-type MEFs revealed genes involved specifically in early regulation of the adipocyte differentiation as well as secreted factors and signaling molecules regulating the later phase of differentiation. In an attempt to identify transcription factors regulating adipogenesis, bioinformatics analysis of the promoters of coordinately and highly expressed genes was performed. We were able to identify a number of high-confidence target genes for follow-up experimental studies. Additionally, combination of experimental data and computational analyses pinpointed a feedback-loop between Pparg and Foxo1.To analyze the effects of the retinoblastoma protein at the transcriptional level we chose a perturbated system (Rb-/- MEFs) for comparison to the transcriptional program of wild-type MEFs. Gene ontology analysis of 64 deregulated genes showed that the Rb-/- MEF model exhibits a brown(-like) adipocyte phenotype. Additionally, the analysis results indicate a different or additional role for pRb family member involvement in the lineage commitment.
  
  
  CONCLUSIONS
  In this study a number of commonly modulated genes during adipogenesis in 3T3-L1 cells and MEFs, potential transcriptional regulation mechanisms, and differentially regulated targets during adipocyte differentiation of Rb-/- MEFs could be identified. These data and the analysis provide a starting point for further experimental studies to identify target genes for pharmacological intervention and ultimately remodeling of white adipose tissue into brown adipose tissue.
authors: Biocenter, Division of Bioinformatics, Innsbruck Medical University, Austria. hubert.hackl@i-med.ac.at.
authors: Robab
authors: R
authors: Hakim-Weber
authors: Anne-M
authors: AM
authors: Krogsdam
authors: Claus
authors: C
authors: Jørgensen
authors: Maria
authors: M
authors: Fischer
authors: Andreas
authors: A
authors: Prokesch
authors: Juliane G
authors: JG
authors: Bogner-Strauss
authors: Stefan R
authors: SR
authors: Bornstein
authors: Jacob B
authors: JB
authors: Hansen
authors: Lise
authors: L
authors: Madsen
authors: Karsten
authors: K
authors: Kristiansen
authors: Zlatko
authors: Z
authors: Trajanoski
authors: Hubert
authors: H
authors: Hackl
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