Faculty Collaboration Database

Involvement of Sp1 elements in the promoter activity of the alpha1-proteinase inhibitor gene. J Biol Chem 1998 Apr 17;273(16):9959-65

Date

05/23/1998

Pubmed ID

9545340

DOI

10.1074/jbc.273.16.9959

Scopus ID

2-s2.0-0032540220 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

The transcripts of the alpha1-proteinase inhibitor in the cornea are different from those in hepatocytes and monocytes, suggesting that alpha1-proteinase inhibitor gene transcription may respond to different cell-specific regulatory mechanisms. Although information on alpha1-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 Sp1-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 corneal cell-specific. The promoter activity in the corneal cells was repressed when Sp1 was coexpressed. In the cornea-thinning disease keratoconus, down-regulation of the alpha1-proteinase inhibitor gene and increased Sp1 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 Sp1 gene. This information may help elucidate the molecular pathways leading to the altered alpha1-proteinase inhibitor expression in keratoconus.

Author List

Li Y, Zhou L, Twining SS, Sugar J, Yue BY

Author

Sally S. Twining PhD Assistant Dean, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Base Sequence
Cells, Cultured
Cloning, Molecular
Cornea
DNA Footprinting
Deoxyribonuclease I
Exons
Gene Expression Regulation
Humans
Liver
Molecular Sequence Data
Promoter Regions, Genetic
Skin
Sp1 Transcription Factor
Stromal Cells
Transcription, Genetic
alpha 1-Antitrypsin