β2-Glycoprotein I (β2-GPI) is a plasma glycoprotein primarily synthesized in the liver. The interindividual variability of β2-GPI expression in subjects with various metabolic syndromes and disease states suggests that it may have clinical importance. However, the regulation of β2-GPI gene expression has not been clarified. To gain more insight into the control of β2-GPI gene expression, we cloned the 4.1-kb 5´-flanking region and characterized the proximal promoter of the β2-GPI gene in this study. Cis-acting elements required for β2-GPI promoter activity were identified with transient transfection assays in the hepatoma cell lines HepG2 and Huh7 and in non-hepatic HeLa cells. Serial deletion analyses of the β2-GPI 5´-flanking sequence revealed that the region from −197 to +7 had strong promoter activity in hepatoma cells but not in HeLa cells. Truncation and site-directed mutagenesis of putative cis-elements within this region showing an atypical TATA box and a HNF-1 (hepatic nuclear factor-1) element were both essential for the β2-GPI promoter activity. Subsequent gel mobility shift assays confirmed the interaction of HNF-1α with the HNF-1 site residing downstream of the TATA box. Co-transfection of β2-GPI promoter-luciferase vector with HNF-1α expression vector in Huh7 and HNF-1-deficient HeLa cells demonstrated the transactivation effect of HNF-1α on β2-GPI promoter activity. In addition, overexpression of HNF-1α enhanced the endogenous β2-GPI expression. These results suggest that the atypical TATA box and HNF-1 cis-element are critical for β2-GPI transcription and HNF-1α may play an important role in cell-specific regulation of β2-GPI gene expression.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
Research Article|
June 01 2004
Cloning and characterization of the human beta2-glycoprotein I (beta2-GPI) gene promoter: roles of the atypical TATA box and hepatic nuclear factor-1alpha in regulating beta2-GPI promoter activity
Hsueh-Hsiao WANG;
Hsueh-Hsiao WANG
Institute of Biochemistry, School of Life Science, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.
Search for other works by this author on:
An-Na CHIANG
An-Na CHIANG
1
Institute of Biochemistry, School of Life Science, National Yang-Ming University, Taipei 112, Taiwan, R.O.C.
1To whom correspondence should be addressed (e-mail [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
October 22 2003
Revision Received:
February 19 2004
Accepted:
February 25 2004
Accepted Manuscript online:
February 25 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 380 (2): 455–463.
Article history
Received:
October 22 2003
Revision Received:
February 19 2004
Accepted:
February 25 2004
Accepted Manuscript online:
February 25 2004
Citation
Hsueh-Hsiao WANG, An-Na CHIANG; Cloning and characterization of the human beta2-glycoprotein I (beta2-GPI) gene promoter: roles of the atypical TATA box and hepatic nuclear factor-1alpha in regulating beta2-GPI promoter activity. Biochem J 1 June 2004; 380 (2): 455–463. doi: https://doi.org/10.1042/bj20031610
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |