Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock

Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock
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DOI:
10.1101/gad.1092303
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发表时间:
2003-06-15
影响因子:
10.5
通讯作者:
Kageyama, R
Kageyama, R
中科院分区:
生物学1区
文献类型:
--
作者:
Bessho, Y;Hirata, H;Kageyama, R

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Hes7是体节发生所必需的bHLH基因,在有体前中胚层(PSM)中显示mRNA的周期性表达。在这里,我们表明,Hes7蛋白也以动态的方式表达,这取决于蛋白酶体介导的降解。空间比较显示,Hes7和Lunatic fringe(Lfng)转录发生在Hes7蛋白阴性结构域。此外,Hes 7和Lfng转录在Hes 7蛋白不存在的情况下组成性上调,并通过Hes 7蛋白的稳定而下调。因此,Hes7蛋白的周期性抑制对于Hes7和Lfng的循环转录至关重要,并且这种负反馈代表了分段时钟的分子基础。
Hes7, a bHLH gene essential for somitogenesis, displays cyclic expression of mRNA in the presomitic mesoderm (PSM). Here, we show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed that Hes7 and Lunatic fringe (Lfng) transcription occurs in the Hes7 protein-negative domains. Furthermore, Hes7 and Lfng transcription is constitutively up-regulated in the absence of Hes7 protein and down-regulated by stabilization of Hes7 protein. Thus, periodic repression by Hes7 protein is critical for the cyclic transcription of Hes7 and Lfng, and this negative feedback represents a molecular basis for the segmentation clock.