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The Journal of Lipid Research, Vol. 39, 255-267, February 1998
Copyright © 1998 by Lipid Research, Inc.


Original Article

Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil

William S. Mohana, Zhang-Qun Chena, Xia Zhanga, Kamel Khalilib, Tasuku Honjoc, Roger G. Deeleya, and Shui-Pang Tama
a Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6
b Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-6799
c Department of Medical Chemistry, Kyoto University Faculty of Medicine, Centre for Molecular Biology and Genetics, Sakyo-ku, 606-01, Japan

Correspondence to: Shui-Pang Tam.

Previously, we demonstrated that protein–DNA interactions at the drug response element (DRE) in the human apoA-I promoter were important for the induction of apoA-I gene expression by gemfibrozil. We now report the cloning and characterization of a DRE transactivating factor. The cloned protein is identical to the putative helicase and potential transcription factor human S mu binding protein-2 (HSµBP2). It is also related to glial factor-1 (GF1), an incomplete version of HSµBP2 lacking the first 494 and the last 128 amino acids. Gel mobility shift assays demonstrated that HSµBP2 binds apoA-I DRE oligomers and forms a specific protein–DNA complex. Northern blot analysis showed that HSµBP2 mRNA is expressed at various levels in a wide range of human tissues. Transient cotransfection experiments performed in HepG2 cells demonstrated that overexpression of HSµBP2 or GF1 induced apoA-I proximal promoter activity by 3-fold and that the apoA-I DRE was necessary for transactivation. Additionally, we demonstrated that transactivation was increased a further 2- to 3-fold by exposing the cells to gemfibrozil.

Together these observations indicate that HSµBP2 acts as a transcription factor that regulates apoA-I gene expression in hepatoma cells and whose activity may be stimulated by gemfibrozil treatment.—Mohan, W. S., Z-Q. Chen, X. Zhang, K. Khalili, T. Honjo, R. G. Deeley, and S-P. Tam. Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil. J. Lipid Res. 1998. 39: 255–267.

Supplementary key words: apolipoprotein A-I, gemfibrozil, gene expression, regulatory sequence, transcription factor


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