[Transcriptional regulation of the endothelial cell-specific receptor, Robo4].
[Transcriptional regulation of the endothelial cell-specific receptor, Robo4].
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DOI：
10.1248/yakushi.132.1045
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Yoshiaki Okada
中科院分区：
文献类型：
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作者：
Yoshiaki Okada
Roundabout4 （Robo4）是一种跨膜受体，属于神经细胞粘附分子Robo家族。Robo4已被证明在内皮细胞（EC）迁移、增殖、血管生成和稳定血管系统中发挥作用。Robo4在发育中的胚胎、胎盘、肿瘤和正常组织的ECs中特异性表达。我们的研究目的是了解Robo4基因表达的机制。在之前的研究中，我们证明了ec特异性Robo4基因的表达是由人类Robo4基因5'侧区域的3kb Robo4启动子调控的。体外研究表明，转录因子ga结合蛋白（GABP）和SP1分别通过ETS结合位点-119和2个SP1结合位点-42和-153激活了Robo4启动子。这些位点的功能相关性通过在小鼠中使用Hprt位点敲入的体内报告基因检测得到证实。除了转录因子的调控机制外，我们最近的研究表明启动子的表观遗传修饰有助于Robo4基因的表达。本文将讨论转录因子和表观遗传调控对Robo4基因表达的调控机制。
Roundabout4 (Robo4) is a transmembrane receptor that belongs to the Robo family of neural cell adhesion molecules. Robo4 has been shown to play a role in endothelial cell (EC) migration, proliferation, angiogenesis, and stabilizing the vasculature. Robo4 is expressed specifically in ECs in the developing embryo, placenta, tumors, and normal tissues. The goal of our study is to understand the mechanism for Robo4 gene expression. In the previous study we demonstrated that EC-specific Robo4 gene expression was regulated by the 3-kb Robo4 promoter in the 5'-flanking region of the human Robo4 gene. In vitro studies demonstrated that the Robo4 promoter is activated by the transcription factors GA-binding protein (GABP) and SP1 through the ETS binding site at -119 and the 2 SP1 binding sites at -42 and -153, respectively. The functional relevance of these sites was confirmed by in vivo reporter gene assays using Hprt locus knock in mice. In addition to the regulation mechanism by transcription factors, our recent study implicated that epigenetic modification of the promoter contributes to the Robo4 gene expression. Here I will discuss the regulation mechanism of Robo4 gene expression by transcription factors and epigenetic control.