Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China.
BMC Genet. 2010 Feb 8;11:12. doi: 10.1186/1471-2156-11-12.
LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms. However, how the expression of human LRP5 gene is regulated remains unclear.
In order to characterize the transcriptional regulation of human LRP5 gene, we cloned the 5' flanking region and evaluated its transcriptional activity in a luciferase reporter system. We demonstrated that both KLF15 and Sp1 binding sites between -72 bp and -53 bp contribute to the transcriptional activation of human LRP5 promoter. Chromatin immunoprecipitation assay demonstrated that the ubiquitous transcription factors KLF15 and Sp1 bind to this region. Using Drosophila SL2 cells, we showed that KLF15 and Sp1 trans-activated the LRP5 promoter in a manner dependent on the presence of Sp1-binding and KLF15-binding motifs.
Both KLF15 and Sp1 binding sites contribute to the basal activity of human LRP5 promoter. This study provides the first insight into the mechanisms by which transcription of human LRP5 gene is regulated.
LRP5 是低密度脂蛋白受体超家族的成员，它在胚胎发生过程中调节多种发育过程，并在成年生物体中维持生理内稳态。然而，人类 LRP5 基因的表达如何受到调节仍不清楚。
为了研究人类 LRP5 基因的转录调控，我们克隆了其 5'侧翼区，并在荧光素酶报告基因系统中评估了其转录活性。我们证明了-72 bp 至-53 bp 之间的 KLF15 和 Sp1 结合位点有助于人类 LRP5 启动子的转录激活。染色质免疫沉淀实验表明，普遍存在的转录因子 KLF15 和 Sp1 结合到该区域。使用 Drosophila SL2 细胞，我们表明 KLF15 和 Sp1 通过依赖 Sp1 结合和 KLF15 结合基序的方式转激活 LRP5 启动子。
KLF15 和 Sp1 结合位点均有助于人类 LRP5 启动子的基础活性。本研究首次深入了解了人类 LRP5 基因转录调控的机制。
