Zolfaghari Reza, Ross A Catharine
Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Arch Biochem Biophys. 2009 Sep;489(1-2):1-9. doi: 10.1016/j.abb.2009.08.001. Epub 2009 Aug 8.
Lecithin:retinol acyltransferase (LRAT) is essential for vitamin A storage. Nuclear run-on assays demonstrated transcriptional regulation of the Lrat gene in vivo by all-trans-retinoic acid (RA) and other retinoids. Analysis of a 2.5 kb segment of rat genomic DNA revealed that the region approximately 300 bp upstream from the transcription start site (TSS) is necessary for high luciferase (Luc) reporter activity in HEK293T and HepG2 cells. Although this region lacks retinoid receptor binding elements, it responded to the nuclear receptors RARalpha, RARbeta or RARgamma, with RXRalpha, with and without ligand. Removal of -111 bp from the TSS, which is well conserved in human, rat and mouse genomes, completely eliminated activity. This region contains several basic elements (TATA box, SP3 site, AP-1 site, CAAT box), all of which were essential. Nuclear extracts from RA-treated cells exhibited enhanced binding. Therefore, this proximal region together with basal transcription factors may be sufficient to drive Lrat expression.
视黄醇酰基转移酶（LRAT）对维生素A的储存至关重要。核转录分析表明，全反式视黄酸（RA）和其他类视黄醇在体内对Lrat基因具有转录调控作用。对大鼠基因组DNA的一个2.5 kb片段进行分析发现，转录起始位点（TSS）上游约300 bp的区域对于HEK293T和HepG2细胞中的高荧光素酶（Luc）报告基因活性是必需的。尽管该区域缺乏类视黄醇受体结合元件，但无论有无配体，它都能与核受体RARα、RARβ或RARγ以及RXRα发生反应。从TSS去除在人类、大鼠和小鼠基因组中高度保守的-111 bp，会完全消除活性。该区域包含几个基本元件（TATA框、SP3位点、AP-1位点、CAAT框），所有这些元件都是必需的。来自RA处理细胞的核提取物显示出增强的结合。因此，这个近端区域与基础转录因子一起可能足以驱动Lrat的表达。
