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 Godbout, R Articles by Tilghman, S M Search for Related Content PubMed PubMed Citation Articles by Godbout, R Articles by Tilghman, S M

 Previous Article  |  Next Article 

Mol Cell Biol. 1986 February; 6(2): 477-487

Multiple regulatory elements in the intergenic region between the alpha-fetoprotein and albumin genes.

ABSTRACT

Three enhancer elements spanning a distance of 7 kilobases have been found at the 5' end of the alpha-fetoprotein (AFP) gene. These elements were identified by transient expression assay after the introduction of a modified mouse AFP gene with variable amounts of 5' flanking sequence into a human hepatoma cell line, Hep G2. These regulatory elements function in a position-independent and orientation-independent manner that is typical of enhancers. All three elements will stimulate transcription from the promoter of the herpes simplex virus thymidine kinase gene. In Hep G2 cells, transcriptional activation from the heterologous promoter was approximately 25- to 50-fold higher than the basal levels obtained in the absence of AFP enhancer elements. In HeLa cells, the increase in thymidine kinase gene transcription varied from 6- to 14-fold, indicating that the enhancer elements exhibit some cell type specificity. Deletion analysis of the region proximal to the AFP transcription initiation site identified an essential region between 85 and 52 bases upstream of the site of initiation of transcription whose removal resulted in almost complete extinction of transcriptional activity. This region, which has been shown to be dispensable for transcription in HeLa cells, defines a second tissue-specific regulatory region in the gene.

This article has been cited by other articles:

• Xie, Z., Zhang, H., Tsai, W., Zhang, Y., Du, Y., Zhong, J., Szpirer, C., Zhu, M., Cao, X., Barton, M. C., Grusby, M. J., Zhang, W. J. (2008). Zinc finger protein ZBTB20 is a key repressor of alpha-fetoprotein gene transcription in liver. Proc. Natl. Acad. Sci. USA 105: 10859-10864 [Abstract] [Full Text]  
• Hiroki, T., Song, Y.-H., Liebhaber, S. A., Cooke, N. E. (2006). The human vitamin D-binding protein gene contains locus control determinants sufficient for autonomous activation in hepatic chromatin.. Nucleic Acids Res 34: 2154-2165 [Abstract] [Full Text]  
• Shimizu, M., Takeshita, A., Tsukamoto, T., Gonzalez, F. J., Osumi, T. (2004). Tissue-Selective, Bidirectional Regulation of PEX11{alpha} and Perilipin Genes through a Common Peroxisome Proliferator Response Element. Mol. Cell. Biol. 24: 1313-1323 [Abstract] [Full Text]  
• Janssen, A., Gressens, P., Grabenbauer, M., Baumgart, E., Schad, A., Vanhorebeek, I., Brouwers, A., Declercq, P. E., Fahimi, D., Evrard, P., Schoonjans, L., Collen, D., Carmeliet, P., Mannaerts, G., Van Veldhoven, P., Baes, M. (2003). Neuronal Migration Depends on Intact Peroxisomal Function in Brain and in Extraneuronal Tissues. J. Neurosci. 23: 9732-9741 [Abstract] [Full Text]  
• Scohy, S., Gabant, P., Szpirer, C., Szpirer, J. (2000). Identification of an enhancer and an alternative promoter in the first intron of the {alpha}-fetoprotein gene. Nucleic Acids Res 28: 3743-3751 [Abstract] [Full Text]  
• Crowe, A. J., Sang, L., Li, K. K., Lee, K. C., Spear, B. T., Barton, M. C. (1999). Hepatocyte Nuclear Factor 3 Relieves Chromatin-mediated Repression of the alpha -Fetoprotein Gene. J. Biol. Chem. 274: 25113-25120 [Abstract] [Full Text]  
• Lee, K. C., Crowe, A. J., Barton, M. C. (1999). p53-Mediated Repression of Alpha-Fetoprotein Gene Expression by Specific DNA Binding. Mol. Cell. Biol. 19: 1279-1288 [Abstract] [Full Text]  
• Magee, T. R., Cai, Y., El-Houseini, M. E., Locker, J., Wan, Y.-J. Y. (1998). Retinoic Acid Mediates Down-regulation of the alpha -Fetoprotein Gene through Decreased Expression of Hepatocyte Nuclear Factors. J. Biol. Chem. 273: 30024-30032 [Abstract] [Full Text]  
• Jin, D. K., Vacher, J., Feuerman, M. H. (1998). alpha -Fetoprotein gene sequences mediating Afr2 regulation during liver regeneration. Proc. Natl. Acad. Sci. USA 95: 8767-8772 [Abstract] [Full Text]  
• Webber, A. L., Tilghman, S. M. (1998). The Absence of Enhancer Competition between Igf2 and H19 following Transfer into Differentiated Cells. Mol. Cell. Biol. 18: 1903-1910 [Abstract] [Full Text]  
• Vacher, J, Tilghman, S. (1990). Dominant negative regulation of the mouse alpha-fetoprotein gene in adult liver. Science 250: 1732-1735 [Abstract]  
• Baumhueter, S, Mendel, D B, Conley, P B, Kuo, C J, Turk, C, Graves, M K, Edwards, C A, Courtois, G, Crabtree, G R (1990). HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF.. Genes Dev. 4: 372-379 [Abstract]  
• Camper, S A, Tilghman, S M (1989). Postnatal repression of the alpha-fetoprotein gene is enhancer independent.. Genes Dev. 3: 537-546 [Abstract]  
• Godbout, R, Tilghman, S M (1988). Configuration of the alpha-fetoprotein regulatory domain during development.. Genes Dev. 2: 949-956 [Abstract]  
• Cereghini, S, Blumenfeld, M, Yaniv, M (1988). A liver-specific factor essential for albumin transcription differs between differentiated and dedifferentiated rat hepatoma cells.. Genes Dev. 2: 957-974 [Abstract]  
• Hayashi, S, Goto, K, Okada, T S, Kondoh, H (1987). Lens-specific enhancer in the third intron regulates expression of the chicken delta 1-crystallin gene.. Genes Dev. 1: 818-828 [Abstract]  
• Babiss, L E, Herbst, R S, Bennett, A L, Darnell, J E (1987). Factors that interact with the rat albumin promoter are present both in hepatocytes and other cell types.. Genes Dev. 1: 256-267 [Abstract]  
• Pinkert, C A, Ornitz, D M, Brinster, R L, Palmiter, R D (1987). An albumin enhancer located 10 kb upstream functions along with its promoter to direct efficient, liver-specific expression in transgenic mice.. Genes Dev. 1: 268-276 [Abstract]  
• Vogt, T., Solter, D, Tilghman, S. (1987). Raf, a trans-acting locus, regulates the alpha-fetoprotein gene in a cell-autonomous manner. Science 236: 301-303 [Abstract]  
• Kelsey, G D, Povey, S, Bygrave, A E, Lovell-Badge, R H (1987). Species- and tissue-specific expression of human alpha 1-antitrypsin in transgenic mice.. Genes Dev. 1: 161-171 [Abstract]  
• Hammer, R., Krumlauf, R, Camper, S., Brinster, R., Tilghman, S. (1987). Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. Science 235: 53-58 [Abstract]  
• Ogden, S. K., Lee, K. C., Barton, M. C. (2000). Hepatitis B Viral Transactivator HBx Alleviates p53-mediated Repression of alpha -Fetoprotein Gene Expression. J. Biol. Chem. 275: 27806-27814 [Abstract] [Full Text]  
• Peyton, D. K., Ramesh, T., Spear, B. T. (2000). Position-dependent activity of alpha -fetoprotein enhancer element III in the adult liver is due to negative regulation. Proc. Natl. Acad. Sci. USA 97: 10890-10894 [Abstract] [Full Text]