Sp1 and KLF15 regulate basal transcription of the human LRP5 gene

Jiangxia Li,Yang Yang,Yaoqin Gong,Yongxin Zou,Baichun Jiang,Xiyu Zhang

doi:10.1186/1471-2156-11-12

Abstract

BackgroundLRP5, 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.ResultsIn 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.ConclusionsBoth 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.

Highlights

LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms
We cloned the 5’ flanking region and evaluated its transcriptional activity in a luciferase reporter system. We demonstrate that both Krüppel-like factor 15(KLF15) and specificity protein 1(Sp1) binding motifs are essential for human LRP5 promoter activity
Several potential transcription factor binding motifs were identified in the promoter region close to transcription start site, including Sp1, KLF15, MZF, MAZ, CDE and ZBPF (Figure. 1B)

Summary

Introduction

LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms. The LRP5 gene, located on human chromosome 11q13, contains 23 exons encoding a 1615 amino acid singlepass transmembrane receptor that belongs to the low density lipoprotein (LDL) receptor superfamily. LRP5 is expressed in multiple adult and embryonic tissues, including bone, macrophages, fat, brain, heart, liver, skin and pancreas, with strongest expression occurring in the liver[1]. In bone, it is expressed by osteoblasts of the endosteal and trabecular bone surfaces but not by osteoclasts[4,5]

Methods

Results

Discussion

Conclusion