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A direct role for C/EBP and the AP-I-binding site in gene expression linked to adipocyte differentiation.

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.

ABSTRACT

Adipocyte differentiation is accompanied by the transcriptional activation of many new genes, including the gene encoding adipocyte P2 (aP2), an intracellular lipid-binding protein. Using specific deletions and point mutations, we have shown that at least two distinct sequence elements in the aP2 promoter contribute to the expression of the chloramphenicol acetyltransferase gene in chimeric constructions transfected into adipose cells. An AP-I site at -120, shown earlier to bind Jun- and Fos-like proteins, serves as a positive regulator of chloramphenicol acetyltransferase gene expression in adipocytes but is specifically silenced by adjacent upstream sequences in preadipocytes. Sequences upstream of the AP-I site at -140 (termed AE-1) can function as an enhancer in both cell types when linked to a viral promoter but can stimulate expression only in fat cells in the intact aP2 promoter. The AE-1 sequence binds an adipocyte protein identical or very closely related to an enhancer-binding protein (C/EBP) that has been previously implicated in the regulation of several liver-specific genes. A functional role for C/EBP in the regulation of the aP2 gene is indicated by the facts that C/EBP mRNA is induced during adipocyte differentiation and the aP2 promoter is transactivated by cotransfection of a C/EBP expression vector into preadipose cells. These results indicate that sequences that bind C/EBP and the Fos-Jun complex play major roles in the expression of the aP2 gene during adipocyte differentiation and demonstrate that C/EBP can directly regulate cellular gene expression.

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• Tang, Q.-Q., Otto, T. C., Lane, M. D. (2003). Mitotic clonal expansion: A synchronous process required for adipogenesis. Proc. Natl. Acad. Sci. USA 100: 44-49 [Abstract] [Full Text]  
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• Tang, Q.-Q., Jiang, M.-S., Lane, M. D. (1999). Repressive Effect of Sp1 on the C/EBPalpha Gene Promoter: Role in Adipocyte Differentiation. Mol. Cell. Biol. 19: 4855-4865 [Abstract] [Full Text]  
• He, G.-P., Kim, S., Ro, H.-S. (1999). Cloning and Characterization of a Novel Zinc Finger Transcriptional Repressor. A DIRECT ROLE OF THE ZINC FINGER MOTIF IN REPRESSION. J. Biol. Chem. 274: 14678-14684 [Abstract] [Full Text]  
• Smas, C. M., Kachinskas, D., Liu, C.-M., Xie, X., Dircks, L. K., Sul, H. S. (1998). Transcriptional Control of the pref-1 Gene in 3T3-L1 Adipocyte Differentiation. SEQUENCE REQUIREMENT FOR DIFFERENTIATION-DEPENDENT SUPPRESSION. J. Biol. Chem. 273: 31751-31758 [Abstract] [Full Text]  
• Lekstrom-Himes, J., Xanthopoulos, K. G. (1998). Biological Role of the CCAAT/Enhancer-binding Protein Family of Transcription Factors. J. Biol. Chem. 273: 28545-28548 [Abstract] [Full Text]  
• Petrovick, M. S., Hiebert, S. W., Friedman, A. D., Hetherington, C. J., Tenen, D. G., Zhang, D.-E. (1998). Multiple Functional Domains of AML1: PU.1 and C/EBPalpha Synergize with Different Regions of AML1. Mol. Cell. Biol. 18: 3915-3925 [Abstract] [Full Text]  
• Roesler, W. J., Park, E. A., McFie, P. J. (1998). Characterization of CCAAT/Enhancer-binding Protein alpha  as a Cyclic AMP-responsive Nuclear Regulator. J. Biol. Chem. 273: 14950-14957 [Abstract] [Full Text]  
• Tang, Q.-Q., Jiang, M.-S., Lane, M. D. (1997). Repression of transcription mediated by dual elements in the CCAAT/enhancer binding protein alpha  gene. Proc. Natl. Acad. Sci. USA 94: 13571-13575 [Abstract] [Full Text]  
• Hollenberg, A. N., Susulic, V. S., Madura, J. P., Zhang, B., Moller, D. E., Tontonoz, P., Sarraf, P., Spiegelman, B. M., Lowell, B. B. (1997). Functional Antagonism between CCAAT/Enhancer Binding Protein-alpha and Peroxisome Proliferator-activated Receptor-gamma on the Leptin Promoter. J. Biol. Chem. 272: 5283-5290 [Abstract] [Full Text]  
• Tai, T.-A. C., Jennermann, C., Brown, K. K., Oliver, B. B., MacGinnitie, M. A., Wilkison, W. O., Brown, H. R., Lehmann, J. M., Kliewer, S. A., Morris, D. C., Graves, R. A. (1996). Activation of the Nuclear Receptor Peroxisome Proliferator-activated Receptor gamma Promotes Brown Adipocyte Differentiation. J. Biol. Chem. 271: 29909-29914 [Abstract] [Full Text]  
• Flodby, P., Barlow, C., Kylefjord, H., Ahrlund-Richter, L., Xanthopoulos, K. G. (1996). Increased Hepatic Cell Proliferation and Lung Abnormalities in Mice Deficient in CCAAT/Enhancer Binding Protein alpha. J. Biol. Chem. 271: 24753-24760 [Abstract] [Full Text]  
• Kim, J B, Spiegelman, B M (1996). ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.. Genes Dev. 10: 1096-1107 [Abstract]  
• Brun, R P, Tontonoz, P, Forman, B M, Ellis, R, Chen, J, Evans, R M, Spiegelman, B M (1996). Differential activation of adipogenesis by multiple PPAR isoforms.. Genes Dev. 10: 974-984 [Abstract]  
• Diehl, A. M., Johns, D. C., Yang, S., Lin, H., Yin, M., Matelis, L. A., Lawrence, J. H. (1996). Adenovirus-mediated Transfer of CCAAT/Enhancer-binding Protein-alpha Identifies a Dominant Antiproliferative Role for This Isoform in Hepatocytes. J. Biol. Chem. 271: 7343-7350 [Abstract] [Full Text]  
• Long, S. D., Pekala, P. H. (1996). Regulation of GLUT4 Gene Expression by Arachidonic Acid. J. Biol. Chem. 271: 1138-1144 [Abstract] [Full Text]  
• He, Y., Chen, H., Quon, M. J., Reitman, M. (1995). The Mouse obese Gene. J. Biol. Chem. 270: 28887-28891 [Abstract] [Full Text]  
• Roesler, W. J., Graham, J. G., Kolen, R., Klemm, D. J., McFie, P. J. (1995). The cAMP Response Element Binding Protein Synergizes with Other Transcription Factors to Mediate cAMP Responsiveness. J. Biol. Chem. 270: 8225-8232 [Abstract] [Full Text]  
• Tontonoz, P, Hu, E, Graves, R A, Budavari, A I, Spiegelman, B M (1994). mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.. Genes Dev. 8: 1224-1234 [Abstract]  
• Smyth, M., Sparks, R., Wharton, W (1993). Proadipocyte cell lines: models of cellular proliferation and differentiation. J. Cell Sci. 106: 1-9  
• Oliviero, S, Robinson, G S, Struhl, K, Spiegelman, B M (1992). Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation.. Genes Dev. 6: 1799-1809 [Abstract]  
• Lin, F T, Lane, M D (1992). Antisense CCAAT/enhancer-binding protein RNA suppresses coordinate gene expression and triglyceride accumulation during differentiation of 3T3-L1 preadipocytes.. Genes Dev. 6: 533-544 [Abstract]  
• Metz, R, Ziff, E (1991). cAMP stimulates the C/EBP-related transcription factor rNFIL-6 to trans-locate to the nucleus and induce c-fos transcription.. Genes Dev. 5: 1754-1766 [Abstract]  
• Williams, S C, Cantwell, C A, Johnson, P F (1991). A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro.. Genes Dev. 5: 1553-1567 [Abstract]  
• Graves, R A, Tontonoz, P, Ross, S R, Spiegelman, B M (1991). Identification of a potent adipocyte-specific enhancer: involvement of an NF-1-like factor.. Genes Dev. 5: 428-437 [Abstract]  
• Umek, R., Friedman, A., McKnight, S. (1991). CCAAT-enhancer binding protein: a component of a differentiation switch. Science 251: 288-292 [Abstract]  
• Dowell, P., Flexner, C., Kwiterovich, P. O., Lane, M. D. (2000). Suppression of Preadipocyte Differentiation and Promotion of Adipocyte Death by HIV Protease Inhibitors. J. Biol. Chem. 275: 41325-41332 [Abstract] [Full Text]  
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