Axial (HNF3 beta) and retinoic acid receptors are regulators of the zebrafish sonic hedgehog promoter
Axial (HNF3 beta) and retinoic acid receptors are regulators of the zebrafish sonic hedgehog promoter
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DOI：
10.1093/emboj/16.13.3955
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发表时间：
1997-07-01
期刊：
影响因子：
11.4
通讯作者：
Strahle, U
中科院分区：
文献类型：
--
作者：
Chang, BE;Blader, P;Strahle, U
信号分子Sonic hedgehog在脊椎动物胚胎发生过程中参与了许多不同的模式化过程。在斑马鱼胚胎的初生体轴中，音刺猬与轴（哺乳动物中的HNF 3 β）共表达，轴是有翼螺旋家族的转录调节因子。我们在这里表明，轴的错误表达导致异位激活的音刺猬表达的斑马鱼，这表明轴是一个调节器的音刺猬转录。从斑马鱼中克隆了音刺猬基因，其启动子的特征在于轴向激活。轴向或大鼠HNF 3 β的表达。结果共转染的音刺猬启动子-CAT融合基因被激活。这种效应由两个轴向（HNF 3 β）识别序列介导。我们还在音刺猬上游区域鉴定了一个视黄酸反应元件（RARE），该元件可以在体外与视黄酸受体（RAR）和类维生素A X受体（RXR）异二聚体结合，并赋予视黄酸对HeLa细胞系统中音刺猬启动子的诱导性。我们的研究结果表明，轴（HNF 3 β）和视黄酸受体是音刺猬基因的直接调节因子。
The signalling molecule Sonic hedgehog is involved in a multitude of distinct patterning processes during vertebrate embryogenesis. In the nascent body axis of the zebrafish embryo, sonic hedgehog is co-expressed with axial (HNF3 beta in mammals), a transcription regulator of the winged helix family. We show here that misexpression of axial leads to ectopic activation of sonic hedgehog expression in the zebrafish, suggesting that axial is a regulator of sonic hedgehog transcription. The sonic hedgehog gene was cloned from zebrafish and its promoter was characterized with respect to activation by axial. Expression of axial or rat HNF3 beta. in HeLa cells results in activation of co-transfected sonic hedgehog promoter-CAT fusion genes. This effect is mediated by two Axial (HNF3 beta) recognition sequences. We furthermore identified a retinoic acid response element (RARE) in the sonic hedgehog upstream region which can be bound by retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers in vitro and confers retinoic acid inducibility to the sonic hedgehog promoter in the HeLa cell system. Our results suggest that both Axial (HNF3 beta) and retinoic acid receptors are direct regulators of the sonic hedgehog gene.