An essential set of basic DNA response elements is required for receptor-dependent transcription of the lecithin:retinol acyltransferase (Lrat) gene.

An essential set of basic DNA response elements is required for receptor-dependent transcription of the lecithin:retinol acyltransferase (Lrat) gene.
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DOI:
10.1016/j.abb.2009.08.001
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发表时间:
2009-09
影响因子:
3.9
通讯作者:
Ross AC
Ross AC
中科院分区:
生物学3区
文献类型:
--
作者:
Zolfaghari R;Ross AC

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LRAT:视黄醇酰基转移酶(LRAT)是维生素A储存所必需的。核运行的分析表明,在体内的Lrat基因的转录调节全反式维甲酸(RA)和其他类维生素A。对大鼠基因组DNA的2.5kb片段的分析表明,转录起始位点(TSS)上游约300 bp的区域是HEK 293 T和HepG 2细胞中高荧光素酶(Luc)报告活性所必需的。尽管该区域缺乏类维生素A受体结合元件,但它对核受体RARα、RARβ或RARγ、RXRα、配体和无配体都有反应。从TSS中去除约111 bp(其在人、大鼠和小鼠基因组中非常保守)完全消除了活性。该区域包含几个基本元件(TATA盒,SP3位点,AP-1位点,CAAT盒),所有这些都是必需的。从RA处理的细胞核提取物表现出增强的结合。因此,该近端区域与基础转录因子一起可能足以驱动Lrat表达。
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 ~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 RARα, RARβ or RARγ, with RXRα, 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.
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