Fatty acid translocase (FAT/CD36) is a cell-surface glycoprotein that functions as a receptor/transporter for long-chain fatty acids (LCFAs), and interacts with other protein and lipid ligands. FAT/CD36 is expressed by various cell types, including platelets, monocytes/macrophages and endothelial cells, and tissues with an active LCFA metabolism, such as adipose, small intestine and heart. FAT/CD36 expression is induced during adipose cell differentiation and is transcriptionally up-regulated by LCFAs and thiazolidinediones in pre-adipocytes via a peroxisome-proliferator-activated receptor (PPAR)-mediated process. We isolated and analysed the murine FAT/CD36 promoter employing C2C12N cells directed to differentiate to either adipose or muscle. Transient transfection studies revealed that the 309bp upstream from the start of exon 1 confer adipose specific activity. Sequence analysis of this DNA fragment revealed the presence of two imperfect direct repeat-1 elements. Electrophoretic mobility-shift assay demonstrated that these elements were peroxisome-proliferator-responsive elements (PPREs). Mutagenesis and transfection experiments indicated that both PPREs co-operate to drive strong promoter activity in adipose cells. We conclude that murine FAT/CD36 expression in adipose tissue is dependent upon transcriptional activation via PPARs through binding to two PPREs located at −245 to −233bp and −120 to −108bp from the transcription start site.
Structural and functional characterization of the mouse fatty acid translocase promoter: activation during adipose differentiation
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Lydia TEBOUL, Maria FEBBRAIO, Danielle GAILLARD, Ez-Zoubir AMRI, Roy SILVERSTEIN, Paul A. GRIMALDI; Structural and functional characterization of the mouse fatty acid translocase promoter: activation during adipose differentiation. Biochem J 1 December 2001; 360 (2): 305–312. doi: https://doi.org/10.1042/bj3600305
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