Multiple levels of transcriptional and post-transcriptional regulation are required to define the domain of Hoxb4 expression
Multiple levels of transcriptional and post-transcriptional regulation are required to define the domain of Hoxb4 expression
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DOI：
10.1242/dev.00471
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发表时间：
2003-06-01
期刊：
影响因子：
4.6
通讯作者：
Rigby, PWJ
中科院分区：
文献类型：
--
作者：
Brend, T;Gilthorpe, J;Rigby, PWJ
HOX基因是动物胚胎前后模式的关键决定因素，而这些基因的空间受限表达对这一功能至关重要。在这项研究中，我们证明了HOXB4在小鼠胚胎的近轴中胚层中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在整个胚胎发育过程中维持完整的表达结构域。位于基因内含子(C区)的增强子足以在适当的时间激活表达，并在近轴中胚层(SOMITE 6/7)建立正确的前边界。然而，HOXB4启动子需要在8.5dpc以上保持这种表达。此外，3‘非翻译区(B区)内的序列对于维持自9.0DPC起在体节7中的表达是特别必要的。启动子和B区都不能独立地指导体细胞表达，这表明调控元件的相互作用对于维持HOXB4的中轴旁侧中胚层结构域是至关重要的。我们进一步报道，HOXB4的表达结构域受到调控旁轴中胚层转录稳定性和神经管中蛋白质选择性翻译和/或降解的限制。此外，由于转基因转录物中没有HOXB4 3‘-非翻译序列，导致了一些HOXB4转基因基因在后部体节中的不适当表达，这表明B区中存在对转录和转录后调控都很重要的序列。
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.