Sato Osamu, Takanashi Naoki, Motojima Kiyoto
Department of Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo, 204-8588, Japan.
Mol Cell Biochem. 2007 May;299(1-2):37-43. doi: 10.1007/s11010-005-9035-0. Epub 2006 Apr 28.
Fatty acid translocase (FAT)/CD36 is a multi-functional membrane protein participating in uptake of long-chain fatty acids and oxidized low density lipoprotein, playing an important role in lipid homeostasis. We reported the dual promoter structures of the mouse and human FAT/CD36 genes in relation to the tissue-specific expression and regulation by peroxisome proliferator-activated receptors (PPARs) (Sato et.al. J. Biol. Chem. 277, 15703-15711, 2002). However, these structures alone could not explain a large induction of the mRNA by a PPAR ligand in the mouse intestine. To learn more about the tissue-specific transcriptional regulation of the FAT/CD36 gene for lipid homeostasis at the whole body level, we cloned the cDNA for the induced mRNA in the mouse intestine and identified third promoter close to the first common exon of the gene. The human gene also has essentially the same gene organization. RT-PCR and Northern blot analyses showed that the three promoters are differentially used in various mouse tissues and the cultured human cells. The physiological significance of these complex promoter structures was suggested by the differential responsiveness to a peroxisome proliferator-activated receptor ligand and the differences in translational efficiencies or stabilities of the mRNA among the isoforms.
脂肪酸转运蛋白（FAT）/CD36是一种多功能膜蛋白，参与长链脂肪酸和氧化型低密度脂蛋白的摄取，在脂质稳态中发挥重要作用。我们报道了小鼠和人类FAT/CD36基因的双启动子结构与过氧化物酶体增殖物激活受体（PPARs）介导的组织特异性表达及调控的关系（佐藤等人，《生物化学杂志》，第277卷，第15703 - 15711页，2002年）。然而，仅这些结构无法解释PPAR配体在小鼠肠道中对mRNA的大幅诱导。为了在全身水平上更多地了解FAT/CD36基因对脂质稳态的组织特异性转录调控，我们克隆了小鼠肠道中诱导型mRNA的cDNA，并鉴定出靠近该基因第一个共有外显子的第三个启动子。人类基因也具有基本相同的基因结构。逆转录 - 聚合酶链反应（RT-PCR）和Northern印迹分析表明，这三个启动子在小鼠的各种组织和培养的人类细胞中被差异使用。这些复杂启动子结构的生理意义体现在对过氧化物酶体增殖物激活受体配体的不同反应性以及各亚型mRNA在翻译效率或稳定性上的差异。
