Expression of Fgf15 is regulated by both activator and repressor forms of Gli2 in vitro
Expression of Fgf15 is regulated by both activator and repressor forms of Gli2 in vitro
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DOI：
10.1016/j.bbrc.2008.02.015
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发表时间：
2008-05-02
影响因子：
3.1
通讯作者：
Ishibashi, Makoto
中科院分区：
文献类型：
--
作者：
Komada, Munekazu;Saitsu, Hirotomo;Ishibashi, Makoto
成纤维细胞生长因子15（Fgf 15）在七体节期的间脑和中脑的内侧区表达。在以前的研究中，我们发现，通过Gli蛋白的Sonic hedgehog信号传导是Fgf 15在该区域表达所必需的。Fgf 15的表达结构域与Gli 2的表达结构域重叠，并且GliB结合位点（GliBs）位于Fgf 15基因的3.6-kb 5 '侧翼增强子/启动子区。在这项研究中，我们确定了两个额外的Gli结合位点，称为Gli响应元件（GliREs）。染色质免疫沉淀实验表明Gli 2与GliREs直接结合。荧光素酶测定的结果表明，Gli 2激活剂形式与GliBS结合，Gli 2阻遏物形式与GliRE结合。这些发现表明Gli 2的阻遏物形式优先结合GliRE以控制Fgf 15的表达。(c)2008年爱思唯尔公司All rights reserved.
Fibroblast growth factor 15 (Fgf15) is expressed in the medial region of diencephalon and midbrain by the seven-somite stage. In the previous studies, we showed that Sonic hedgehog signaling through Gli protein is required for Fgf15 expression in this region. The Fgf15 expression domain overlapped with that of Gli2 and the Gli-binding site (GliBs) is located in the 3.6-kb 5'-flanking enhancer/promoter region of the Fgf15 gene. In this study, we identified the two additional Gli-binding sites in row, called Gli-responsive elements (GliREs). Chromatin immunoprecipitation assay indicated that Gli2 directly binds to GliREs. The results from luciferase assays indicated that the Gli2 activator form binds to the GliBS and that the Gli2 repressor form binds to the GliREs. These findings suggest that the repressor form of Gli2 preferentially binds to the GliREs to control Fgf15 expression. (c) 2008 Elsevier Inc. All rights reserved.