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

Abstract

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.

Keywords

• apolipoprotein A-I
• gemfibrozil
• gene expression
• regulatory sequence
• transcription factor