Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins
Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins
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DOI：
10.1101/gad.10.16.2003
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发表时间：
1996-08-15
影响因子：
10.5
通讯作者：
Ingham, PW
中科院分区：
文献类型：
--
作者：
Alexandre, C;Jacinto, A;Ingham, PW
Hedgehog（Hh）分泌蛋白家族的成员最近被鉴定为调节果蝇和脊椎动物发育中各种诱导相互作用的关键信号分子。尽管它们具有广泛的重要性，但Hh信号在细胞内转导的方式仍然知之甚少。在果蝇中介导Hh信号传导的转录因子的最佳候选者是肘中断（ci）基因的产物，其是与脊椎动物GLI基因家族的蛋白质产物具有显著同源性的锌指蛋白。在这里，我们表明，即使在没有hh活性的情况下，升高的Ci水平也足以激活patched（ptc）和其他hh靶基因。我们还表明，Ci可以作为一个转录激活因子在酵母中的功能，并证明锌指结构域的蛋白质是足够的，其目标特异性。最后，我们确定的PTC基因的启动子区，Hh信号的主要目标，是相同的GLI蛋白的共识结合序列，并需要报告基因的表达在响应Hh活性的序列。两者合计，我们的研究结果强烈支持的作用，CI作为转录激活剂，介导HH信号。
Members of the Hedgehog (Hh) family of secreted proteins have been identified recently as key signaling molecules that regulate a variety of inductive interactions central to the development of both Drosophila and vertebrates. Despite their widespread importance, the way in which Hh signals are transduced inside the cell remains poorly understood. The best candidate for a transcription factor that mediates Hh signaling in Drosophila is the product of the cubitus interruptus (ci) gene, a zinc finger protein that exhibits significant homology to protein products of the vertebrate GLI gene family. Here, we show that elevated levels of Ci are sufficient to activate patched (ptc) and other hh target genes, even in the absence of hh activity. We also show that Ci can function as a transcriptional activator in yeast and demonstrate that the zinc finger domain of the protein is sufficient for its target specificity. Finally, we identify sequences in the promoter region of the ptc gene, a primary target of Hh signaling, that are identical to the consensus-binding sequence of the GLI protein and are required for reporter gene expression in response to Hh activity. Taken together, our results strongly support the role for Ci as the transcriptional activator that mediates hh signaling.