Periodic Lunatic fringe expression is controlled during segmentation by a cyclic transcriptional enhancer responsive to notch signaling
Periodic Lunatic fringe expression is controlled during segmentation by a cyclic transcriptional enhancer responsive to notch signaling
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DOI：
10.1016/s1534-5807(02)00211-3
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发表时间：
2002-07-01
影响因子：
11.8
通讯作者：
Ish-Horowicz, D
中科院分区：
文献类型：
--
作者：
Morales, AV;Yasuda, Y;Ish-Horowicz, D
分子振荡器调节脊椎动物分割的速度。在这里，我们表明，振荡器（时钟）控制周期性启动转录的不分节的前体中胚层（PSM）。我们确定了一个进化上保守的2.3 kb区域的小鼠Lunatic边缘（Lfng）的启动子，驱动PSM中的周期性表达。该区域包括增强和抑制环状Lfng转录所需的保守区块，并防止在形成的体节中继续表达。我们还表明，在完全不存在Notch信号的情况下，循环PSM中的动态表达丢失，并且Notch信号直接通过CBF 1/RBP-Jkappa结合位点来调节Lfng。这些结果与振荡Notch信号传导是分割时钟的基础并且直接激活和间接抑制Lfng表达的模型一致。
A molecular oscillator regulates the pace of vertebrate segmentation. Here, we show that the oscillator (clock) controls cyclic initiation of transcription in the unsegmented presomitic mesoderm (PSM). We identify an evolutionarily conserved 2.3 kb region in the murine Lunatic fringe (Lfng) promoter that drives periodic expression in the PSM. This region includes conserved blocks required for enhancing and repressing cyclic Lfng transcription, and to prevent continued expression in formed somites. We also show that dynamic expression in the cycling PSM is lost in the total absence of Notch signaling, and that Notch signaling acts directly via CBF1/RBP-Jkappa binding sites to regulate Lfng. These results are consistent with a model in which oscillatory Notch signaling underlies the segmentation clock and directly activates and indirectly represses Lfng expression.