维甲酸对斑马鱼cyp26a1启动子的调控
Retinoid regulation of the zebrafish cyp26a1 promoter.
作者信息
Hu Ping, Tian Miao, Bao Jie, Xing Guangdong, Gu Xingxing, Gao Xiang, Linney Elwood, Zhao Qingshun
机构信息
Model Animal Research Center, MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, Jiangsu, China.
出版信息
Dev Dyn. 2008 Dec;237(12):3798-808. doi: 10.1002/dvdy.21801.
Cyp26A1 is a major enzyme that controls retinoic acid (RA) homeostasis by metabolizing RA into bio-inactive metabolites. Previous research revealed that the mouse Cyp26A1 promoter has two canonical RA response elements (RAREs) that underlie the regulation of the gene by RA. Analyzing the 2,533-base pairs (2.5 k) genomic sequence upstream of zebrafish cyp26a1 start codon, we report that the two RAREs are conserved in zebrafish cyp26a1 promoter. Mutagenesis demonstrated that the two RAREs work synergistically in RA inducibility of cyp26a1. Fusing the 2.5 k (kilobase pairs) fragment to the enhanced yellow fluorescent protein (eYFP) reporter gene, we have generated two transgenic lines of zebrafish [Tg(cyp26a1:eYFP)]. The transgenic zebrafish display expression patterns similar to that of cyp26a1 gene in vivo. Consistent with the in vitro results, the reporter activity is RA inducible in embryos. Taken together, our results demonstrate that the 2.5 k fragment underlies the regulation of the zebrafish cyp26a1 gene by RA.
Cyp26A1是一种主要的酶，它通过将视黄酸（RA）代谢为生物无活性的代谢产物来控制RA的体内平衡。先前的研究表明，小鼠Cyp26A1启动子有两个典型的RA反应元件（RAREs），它们是RA对该基因进行调控的基础。通过分析斑马鱼cyp26a1起始密码子上游2533个碱基对（2.5 k）的基因组序列，我们发现这两个RAREs在斑马鱼cyp26a1启动子中是保守的。诱变实验表明，这两个RAREs在cyp26a1的RA诱导性中协同发挥作用。将2.5 k（千碱基对）片段与增强型黄色荧光蛋白（eYFP）报告基因融合，我们构建了两个斑马鱼转基因品系[Tg(cyp26a1:eYFP)]。转基因斑马鱼在体内显示出与cyp26a1基因相似的表达模式。与体外实验结果一致，报告基因活性在胚胎中是RA可诱导的。综上所述，我们的结果表明，2.5 k片段是RA对斑马鱼cyp26a1基因进行调控的基础。
Zotero 插件