Alternative promoter usage of the membrane glycoprotein CD36.
BACKGROUND
CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation.


RESULTS
We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters.


CONCLUSIONS
Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.
Andersen
Malin
M
Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology (KTH), 106 91 Stockholm, Sweden. malina@biotech.kth.se
Lenhard
Boris
B
Whatling
Carl
C
Eriksson
Per
P
Odeberg
Jacob
J
D000273:Adipose Tissue / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics*; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009928:Organ Specificity; D010920:Placenta / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D013116:Spinal Cord / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C099252:oxidized low density lipoprotein