Structural and functional characterization of the mouse fatty acid translocase promoter: activation during adipose differentiation.
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 C(2)C(12)N cells directed to differentiate to either adipose or muscle. Transient transfection studies revealed that the 309 bp 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 -233 bp and -120 to -108 bp from the transcription start site.
Teboul
L
L
INSERM U470, Centre de Biochimie, Parc Valrose, UFR Sciences, Université de Nice-Sophia Antipolis, 06108 Nice, France. lteboul@icr.ac.uk
Febbraio
M
M
Gaillard
D
D
Amri
E Z
EZ
Silverstein
R
R
Grimaldi
P A
PA
D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology*; D000818:Animals; D001483:Base Sequence; D018955:CD36 Antigens / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002999:Clone Cells; D003001:Cloning, Molecular; D004789:Enzyme Activation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid / Q000502:physiology; D020218:Response Elements / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D018955:CD36 Antigens; D008562:Membrane Glycoproteins; D027361:Organic Anion Transporters; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors