title: CCAAT/enhancer binding proteins alpha and beta are transcriptional activators of the brown fat uncoupling protein gene promoter.
abstract: Primary brown adipocytes differentiated in culture were transiently transfected with plasmids containing different extensions of the 5'-flanking region of the rat uncoupling protein gene placed upstream of the bacterial chloramphenicol acetyltransferase reporter gene. Co-transfection of expression vectors for CCAAT/enhancer binding protein (C/EBP) alpha and C/EBP beta trans-activated the rat uncoupling protein gene promoter due to sequences in the 5' proximal region. DNAse I footprint analysis showed the presence of two C/EBP binding sites at positions -457/-440 and -335/-318, which interact with purified C/EBP beta as well as with C/EBP proteins present in brown fat or liver nuclear extracts. Two copies of each site placed upstream of the enhancerless SV40 promoter confer C/EBP alpha and C/EBP beta responsiveness to this heterologous promoter when co-transfected into HepG2 cells. It is concluded that the UCP gene is a target for C/EBP-dependent transcriptional regulation. This suggests that the C/EBP family of transcription factors is involved in the establishment of the characteristic phenotype of the brown adipocyte.
authors.affiliation: Department de Bioquímica i Fisiologia, Universitat de Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Yubero
authors.forename: C
authors.initials: C
authors.lastname: Manchado
authors.forename: A M
authors.initials: AM
authors.lastname: Cassard-Doulcier
authors.forename: T
authors.initials: T
authors.lastname: Mampel
authors.forename: O
authors.initials: O
authors.lastname: Viñas
authors.forename: R
authors.initials: R
authors.lastname: Iglesias
authors.forename: M
authors.initials: M
authors.lastname: Giralt
authors.forename: F
authors.initials: F
authors.lastname: Villarroya
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D000071256:Uncoupling Protein 1
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000071256:Uncoupling Protein 1