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Involvement of Sp1 elements in the promoter activity of the α1-proteinase inhibitor gene
被引:30
|作者:
Li, YH
Zhou, LL
Twining, SS
Sugar, J
Yue, BYJT
[1
]
机构:
[1] Univ Illinois, Coll Med, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA
[2] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA
[3] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA
关键词:
D O I:
10.1074/jbc.273.16.9959
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The transcripts of the alpha(1)-proteinase inhibitor in the cornea are different from those in hepatocytes and monocytes, suggesting that alpha(1)-proteinase inhibitor gene transcription may respond to different cell-specific regulatory mechanisms. Although information on alpha(1)-proteinase inhibitor gene structure has been obtained, little is known regarding the cis- and trans-acting factors that regulate its expression. In this study, we cloned and sequenced a 2,7-kilobase 5'-flanking region upstream from the corneal transcription initiation site of the gene, demonstrated functional promoter activity, and identified the regulatory elements. Sequencing revealed that the 5'-flanking element was highly G/C-rich in regions proximal to the corneal transcription start site. DNase I footprinting located 10 potential Spl-binding sites between nucleotides -1519 and +44. The putative promoter was functional in human corneal stromal cells, but not in human skin, scleral, and conjunctival fibroblasts, suggesting that the promoter may be corned cell-specific. The promoter activity in the corneal cells was repressed when Spl was coexpressed. In the cornea-thinning disease keratoconus, down-regulation of the alpha(1)-proteinase inhibitor gene and increased Spl expression have both been demonstrated. The current results suggest that down-regulation of the inhibitor in keratoconus corneas may be related directly to overexpression of the Spl gene. This information may help elucidate the molecular pathways leading to the altered alpha(1)-proteinase inhibitor expression in keratoconus.
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页码:9959 / 9965
页数:7
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