This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yanuka-Kashles, O Articles by Reshef, L Search for Related Content PubMed PubMed Citation Articles by Yanuka-Kashles, O Articles by Reshef, L

 Previous Article  |  Next Article 

Mol Cell Biol. 1994 November; 14(11): 7124-7133

Transcriptional regulation of the phosphoenolpyruvate carboxykinase gene by cooperation between hepatic nuclear factors.

Department of Developmental Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

ABSTRACT

To study the transcriptional regulation of the liver gluconeogenic phenotype, the underdifferentiated mouse Hepa-1c1c7 (Hepa) hepatoma cell line was used. These cells mimicked the fetal liver by appreciably expressing the alpha-fetoprotein and albumin genes but not the phosphoenolpyruvate carboxykinase (PEPCK) gene. Unlike the fetal liver, however, Hepa cells failed to express the early-expressed factors hepatocyte nuclear factor 1 alpha (HNF-1 alpha) and HNF-4 and the late-expressed factor C/EBP alpha, thereby providing a suitable system for examining possible cooperation between these factors in the transcriptional regulation of the PEPCK gene. Transient transfection assays of a chimeric PEPCK-chloramphenicol acetyltransferase construct showed a residual PEPCK promoter activity in the Hepa cell line, which was slightly stimulated by cotransfection with a single transcription factor from either the C/EBP family or HNF-1 alpha but not at all affected by cotransfection of HNF-4. In contrast, cotransfection of the PEPCK construct with members from the C/EBP family plus HNF-1 alpha resulted in a synergistic stimulation of the PEPCK promoter activity. This synergistic effect depended on the presence in the PEPCK promoter region of the HNF-1 recognition sequence and on the presence of two C/EBP recognition sequences. The results demonstrate a requirement for coexistence and cooperation between early and late liver-enriched transcription factors in the transcriptional regulation of the PEPCK gene. In addition, the results suggest redundancy between members of the C/EBP family of transcription factors in the regulation of PEPCK gene expression.

This article has been cited by other articles:

• Rebouissou, S., Imbeaud, S., Balabaud, C., Boulanger, V., Bertrand-Michel, J., Terce, F., Auffray, C., Bioulac-Sage, P., Zucman-Rossi, J. (2007). HNF1{alpha} Inactivation Promotes Lipogenesis in Human Hepatocellular Adenoma Independently of SREBP-1 and Carbohydrate-response Element-binding Protein (ChREBP) Activation. J. Biol. Chem. 282: 14437-14446 [Abstract] [Full Text]  
• Cassuto, H., Kochan, K., Chakravarty, K., Cohen, H., Blum, B., Olswang, Y., Hakimi, P., Xu, C., Massillon, D., Hanson, R. W., Reshef, L. (2005). Glucocorticoids Regulate Transcription of the Gene for Phosphoenolpyruvate Carboxykinase in the Liver via an Extended Glucocorticoid Regulatory Unit. J. Biol. Chem. 280: 33873-33884 [Abstract] [Full Text]  
• Divine, J. K., McCaul, S. P., Simon, T. C. (2003). HNF-1{alpha} and endodermal transcription factors cooperatively activate Fabpl: MODY3 mutations abrogate cooperativity. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G62-G72 [Abstract] [Full Text]  
• Olswang, Y., Blum, B., Cassuto, H., Cohen, H., Biberman, Y., Hanson, R. W., Reshef, L. (2003). Glucocorticoids Repress Transcription of Phosphoenolpyruvate Carboxykinase (GTP) Gene in Adipocytes by Inhibiting Its C/EBP-mediated Activation. J. Biol. Chem. 278: 12929-12936 [Abstract] [Full Text]  
• Ban, N., Yamada, Y., Someya, Y., Miyawaki, K., Ihara, Y., Hosokawa, M., Toyokuni, S., Tsuda, K., Seino, Y. (2002). Hepatocyte Nuclear Factor-1{alpha} Recruits the Transcriptional Co-Activator p300 on the GLUT2 Gene Promoter. Diabetes 51: 1409-1418 [Abstract] [Full Text]  
• Naiki, T., Nagaki, M., Shidoji, Y., Kojima, H., Imose, M., Kato, T., Ohishi, N., Yagi, K., Moriwaki, H. (2002). Analysis of Gene Expression Profile Induced by Hepatocyte Nuclear Factor 4alpha in Hepatoma Cells Using an Oligonucleotide Microarray. J. Biol. Chem. 277: 14011-14019 [Abstract] [Full Text]  
• Farsetti, A., Moretti, F., Narducci, M., Misiti, S., Nanni, S., Andreoli, M., Sacchi, A., Pontecorvi, A. (1998). Orphan Receptor Hepatocyte Nuclear Factor-4 Antagonizes Estrogen Receptor {alpha}-Mediated Induction of Human Coagulation Factor XII Gene. Endocrinology 139: 4581-4589 [Abstract] [Full Text]  
• Song, C. S., Jung, M. H., Kim, S. C., Hassan, T., Roy, A. K., Chatterjee, B. (1998). Tissue-specific and Androgen-repressible Regulation of the Rat Dehydroepiandrosterone Sulfotransferase Gene Promoter. J. Biol. Chem. 273: 21856-21866 [Abstract] [Full Text]  
• Lee, Y.-H., Sauer, B., Gonzalez, F. J. (1998). Laron Dwarfism and Non-Insulin-Dependent Diabetes Mellitus in the Hnf-1alpha Knockout Mouse. Mol. Cell. Biol. 18: 3059-3068 [Abstract] [Full Text]  
• Suh, D.-S., Rechler, M. M. (1997). Hepatocyte Nuclear Factor 1 and the Glucocorticoid Receptor Synergistically Activate Transcription of the Rat Insulin-like Growth Factor Binding Protein-1 Gene. Mol. Endocrinol. 11: 1822-1831 [Abstract] [Full Text]  
• Croniger, C., Trus, M., Lysek-Stupp, K., Cohen, H., Liu, Y., Darlington, G. J., Poli, V., Hanson, R. W., Reshef, L. (1997). Role of the Isoforms of CCAAT/Enhancer-binding Protein in the Initiation of Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription at Birth. J. Biol. Chem. 272: 26306-26312 [Abstract] [Full Text]  
• Roesler, W. J., Crosson, S. M., Vinson, C., McFie, P. J. (1996). The alpha-Isoform of the CCAAT/Enhancer-binding Protein Is Required for Mediating cAMP Responsiveness of the Phosphoenolpyruvate Carboxykinase Promoter in Hepatoma Cells. J. Biol. Chem. 271: 8068-8074 [Abstract] [Full Text]  
• Aguanno, A., Afar, R., Albert, V. R. (1996). Tissue-specific Expression of the Nonneuronal Promoter of the Aromatic L-Amino Acid Decarboxylase Gene Is Regulated by Hepatocyte Nuclear Factor 1. J. Biol. Chem. 271: 4528-4538 [Abstract] [Full Text]