We show that Id (inhibitor of DNA binding) 2 and Id3, dominant negative members of the helix-loop-helix (HLH) family, interact with the adipocyte determination and differentiation factor 1 (ADD1)/sterol regulatory element-binding protein (SREBP) 1c, a transcription factor of the basic HLH-leucine zipper family that controls the expression of several key genes of adipose metabolism. Gel mobility-shift assays performed with in vitro-translated ADD1, Id2 or Id3 proteins and a fatty acid synthase (FAS) promoter oligonucleotide showed evidence for a marked inhibition of the formation of DNA-ADD1 complexes by Id2 or Id3 proteins. Co-immunoprecipitation studies using in vitro-translated proteins demonstrated further the physical interaction of Id and ADD1/SREBP-1c proteins in the absence of DNA. Using the FAS gene as a model of an ADD1-regulated promoter in transiently transfected isolated rat adipocytes or mature 3T3-L1 adipocytes, a potent inhibition of the activity of the FAS-chloramphenicol acetyltransferase reporter gene was observed by overexpression of Id2 or Id3. Reciprocally, co-transfection of Id3 antisense and ADD1 expression vectors in preadipocytes potentiated the ADD1/SREBP-1c effect on the FAS promoter activity. Finally, in the non adipogenic NIH-3T3 cell line, most of the ADD1-mediated trans-activation of the FAS promoter was counteracted by co-transfection of Id2 or Id3 expression vectors. Previous studies have indicated Id gene expression to be down-regulated during adipogenesis [Moldes, Lasnier, Fève, Pairault and Djian (1997) Mol. Cell. Biol. 17, 1796-1804]. We here demonstrated that there was a dramatic rise of Id2 and Id3 mRNA levels when 3T3-L1 adipocytes or isolated rat fat cells were exposed to lipolytic and anti-lipogenic agents, forskolin and isoproterenol. Taken together, our data show that Id products are functionally involved in modulating ADD1/SREBP-1c transcriptional activity, and thus lipogenesis in adipocytes.
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December 1999
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Research Article|
December 08 1999
Functional antagonism between inhibitor of DNA binding (Id) and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1c (ADD1/SREBP-1c) trans-factors for the regulation of fatty acid synthase promoter in adipocytes
Marthe MOLDES;
Marthe MOLDES
*Université Pierre et Marie Curie, UPRES-A 7079 CNRS, Paris, France
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Muriel BOIZARD;
Muriel BOIZARD
†U465 INSERM, 15 rue de l'Ecole de Médecine, 75270 Paris Cedex 06, France
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Xavier LE LIEPVRE;
Xavier LE LIEPVRE
†U465 INSERM, 15 rue de l'Ecole de Médecine, 75270 Paris Cedex 06, France
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Bruno FÈVE;
Bruno FÈVE
*Université Pierre et Marie Curie, UPRES-A 7079 CNRS, Paris, France
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Isabelle DUGAIL;
Isabelle DUGAIL
†U465 INSERM, 15 rue de l'Ecole de Médecine, 75270 Paris Cedex 06, France
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Jacques PAIRAULT
Jacques PAIRAULT
1
*Université Pierre et Marie Curie, UPRES-A 7079 CNRS, Paris, France
1To whom correspondence should be addressed, at Centre de Recherches Biomédicales des Cordeliers, 15 rue de l'Ecole de Médecine 75270 Paris Cedex 06, France (e-mail jpairau@;ccr.jussieu.fr).
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Publisher: Portland Press Ltd
Received:
July 26 1999
Revision Received:
September 14 1999
Accepted:
October 14 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 344 (3): 873–880.
Article history
Received:
July 26 1999
Revision Received:
September 14 1999
Accepted:
October 14 1999
Citation
Marthe MOLDES, Muriel BOIZARD, Xavier LE LIEPVRE, Bruno FÈVE, Isabelle DUGAIL, Jacques PAIRAULT; Functional antagonism between inhibitor of DNA binding (Id) and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1c (ADD1/SREBP-1c) trans-factors for the regulation of fatty acid synthase promoter in adipocytes. Biochem J 15 December 1999; 344 (3): 873–880. doi: https://doi.org/10.1042/bj3440873
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