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首页> 外文期刊>Development >Multiple levels of transcriptional and post-transcriptional regulation are required to define the domain of Hoxb4 expression.
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Multiple levels of transcriptional and post-transcriptional regulation are required to define the domain of Hoxb4 expression.

机译：需要多种水平的转录和转录后调节来定义Hoxb4表达域。

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摘要

Hox genes are key determinants of anteroposterior patterning of animal embryos, and spatially restricted expression of these genes is crucial to this function. In this study, we demonstrate that expression of Hoxb4 in the paraxial mesoderm of the mouse embryo is transcriptionally regulated in several distinct phases, and that multiple regulatory elements interact to maintain the complete expression domain throughout embryonic development. An enhancer located within the intron of the gene (region C) is sufficient for appropriate temporal activation of expression and the establishment of the correct anterior boundary in the paraxial mesoderm (somite 6/7). However, the Hoxb4 promoter is required to maintain this expression beyond 8.5 dpc. In addition, sequences within the 3' untranslated region (region B) are necessary specifically to maintain expression in somite 7 from 9.0 dpc onwards. Neither the promoter nor region B can direct somitic expression independently, indicating that the interaction of regulatory elements is crucial for the maintenance of the paraxial mesoderm domain of Hoxb4 expression. We further report that the domain of Hoxb4 expression is restricted by regulating transcript stability in the paraxial mesoderm and by selective translation and/or degradation of protein in the neural tube. Moreover, the absence of Hoxb4 3'-untranslated sequences from transgene transcripts leads to inappropriate expression of some Hoxb4 transgenes in posterior somites, indicating that there are sequences within region B that are important for both transcriptional and post-transcriptional regulation.
机译：Hox基因是动物胚胎前后模式的关键决定因素，这些基因的空间受限表达对该功能至关重要。在这项研究中，我们证明了Hoxb4在小鼠胚胎近轴中胚层的表达在几个不同的阶段受到转录调控，并且多个调控元件相互作用以在整个胚胎发育过程中维持完整的表达域。位于基因内含子（C区）内的增强子足以适当地暂时激活表达并在近轴中胚层（somite 6/7）中建立正确的前边界。但是，需要Hoxb4启动子来维持该表达超过8.5 dpc。另外，在3'非翻译区（B区）内的序列对于从9.0 dpc起在somite 7中维持表达特别必要。启动子和区域B均不能独立地指导体细胞表达，表明调节元件的相互作用对于维持Hoxb4表达的近轴中胚层结构域至关重要。我们进一步报道，通过调节近轴中胚层中的转录物稳定性和神经管中蛋白质的选择性翻译和/或降解，限制了Hoxb4表达的域。此外，转基因转录本中没有Hoxb4 3'-非翻译序列会导致后半节中某些Hoxb4转基因的不适当表达，这表明B区中存在着对转录和转录后调控均重要的序列。

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