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 Grayson, D R Articles by Darnell, J E Search for Related Content PubMed PubMed Citation Articles by Grayson, D R Articles by Darnell, J E, Jr

 Previous Article  |  Next Article 

Mol Cell Biol. 1988 March; 8(3): 1055-1066

A cell-specific enhancer of the mouse alpha 1-antitrypsin gene has multiple functional regions and corresponding protein-binding sites.

Rockefeller University, New York, New York 10021.

ABSTRACT

We have previously described the isolation and characterization of genomic clones corresponding to the mouse alpha 1-antitrypsin gene (Krauter et al., DNA 5:29-36, 1986). In this report, we have analyzed the DNA sequences upstream of the RNA start site that direct hepatoma cell-specific expression of this gene when incorporated into recombinant plasmids. The 160 nucleotides 5' to the cap site direct low-level expression in hepatoma cells, and sequences between -520 and -160 bp upstream of the RNA start site functioned as a cell-specific enhancer of expression both with the alpha 1-antitrypsin promoter and when combined with a functional beta-globin promoter. Within the enhancer region, three binding sites for proteins present in hepatoma nuclear extracts were identified. The location of each site was positioned, using both methylation protection and methylation interference experiments. Each protein-binding site correlated with a functionally important region necessary for full enhancer activity. These experiments demonstrated a complex arrangement of regulatory elements comprising the alpha 1-antitrypsin enhancer. Significant qualitative differences exist between the findings presented here and the cis-acting elements operative in regulating expression of the human alpha 1-antitrypsin gene (Ciliberto et al., Cell 41:531-540, 1985; De Simone et al., EMBO J. 6:2759-2766, 1987).

This article has been cited by other articles:

• Chen, Y., Sharma, R. P., Costa, R. H., Costa, E., Grayson, D. R. (2002). On the epigenetic regulation of the human reelin promoter. Nucleic Acids Res 30: 2930-2939 [Abstract] [Full Text]  
• Li, Y., Zhou, L., Twining, S. S., Sugar, J., Yue, B. Y. J. T. (1998). Involvement of Sp1 Elements in the Promoter Activity of the alpha 1-Proteinase Inhibitor Gene. J. Biol. Chem. 273: 9959-9965 [Abstract] [Full Text]  
• Ray, A., Gao, X., Ray, B. K. (1995). Role of a Distal Enhancer Containing a Functional NF-kappaB-binding Site in Lipopolysaccharide-induced Expression of a Novel alpha(1)-Antitrypsin Gene. J. Biol. Chem. 270: 29201-29208 [Abstract] [Full Text]  
• Fukuda, K, Ishii, Y, Saiga, H, Shiokawa, K, Yasugi, S (1994). Mesenchymal regulation of epithelial gene expression in developing avian stomach: 5'-flanking region of pepsinogen gene can mediate mesenchymal influence on its expression. Development 120: 3487-3495 [Abstract]  
• Wu, R., Galvin, S, Wu, S., Xu, C, Blumenberg, M, Sun, T. (1993). A 300 bp 5'-upstream sequence of a differentiation-dependent rabbit K3 keratin gene can serve as a keratinocyte-specific promoter. J. Cell Sci. 105: 303-316 [Abstract]  
• Bulla, G A, DeSimone, V, Cortese, R, Fournier, R E (1992). Extinction of alpha 1-antitrypsin gene expression in somatic cell hybrids: evidence for multiple controls.. Genes Dev. 6: 316-327 [Abstract]