Short upstream region drives dynamic expression of hypoxia-inducible factor 1alpha during Xenopus development.
Short upstream region drives dynamic expression of hypoxia-inducible factor 1alpha during Xenopus development.
复制标题
短上游区域驱动爪蟾发育过程中缺氧诱导因子 1α 的动态表达。
DOI：
10.1002/dvdy.20049
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Saha,MargaretS
中科院分区：
文献类型：
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作者：
Sipe,ConorW;Gruber,ErikaJ;Saha,MargaretS
缺氧诱导因子 1α (HIF-1α) 在调节氧依赖性基因表达中发挥核心作用，并参与一系列与细胞存活、增殖和发育有关的途径。虽然 HIF-1α 的翻译后调控已得到很好的表征，但其在发育过程中转录水平控制的相对重要性仍不太清楚。尽管已经对小鼠和人类启动子区域进行了体外分析，但迄今为止，还没有对任何脊椎动物 HIF-1α 启动子进行体内分析。为了研究两栖动物非洲爪蟾发育过程中 HIF-1α 的转录调控，我们描述了该基因的表达模式并分离了 xHIF-1α 上游调控区。我们发现 xHIF-1α mRNA 在整个胚胎发生过程中以低水平组成型表达，但在原肠胚阶段以及随后在中枢神经系统和中轴组织的特定区域中显着上调。我们使用一系列截短的 xHIF-1α 启动子构建体进行的功能分析表明，近端启动子的 173 bp 区域在五个等位基因变体中 100% 保守，足以驱动转基因胚胎中的正确表达。尽管这些结果得到了非洲爪蟾细胞系中一组平行体外转染实验的证实，但一些关键差异表明结合体外测定使用转基因方法的重要性。发展动力学 230:229–238, 2004。© 2004 Wiley‐Liss, Inc.
Hypoxia‐inducible factor 1α (HIF‐1α) plays a central role in regulating oxygen‐dependent gene expression and is involved in a range of pathways implicated in cellular survival, proliferation, and development. While the posttranslational regulation of HIF‐1α is well characterized, the relative importance of its control at the transcriptional level during development remains less clear. Although the mouse and human promoter regions have been analyzed in vitro, to date, there has been no in vivo analysis of any vertebrate HIF‐1α promoter. To investigate the transcriptional regulation of HIF‐1α during development of the amphibianXenopus laevis, we have described the gene's expression pattern and isolated the xHIF‐1α upstream regulatory regions. We show xHIF‐1α mRNA to be constitutively expressed at low levels throughout embryogenesis, but with significant up‐regulation during gastrula stages, and subsequently, in specific regions of the central nervous system and axial tissues. Our functional analysis using a series of truncated xHIF‐1α promoter constructs demonstrates that a 173‐bp region of the proximal promoter, which is 100% conserved among five allelic variants, is sufficient to drive correct expression in transgenic embryos. Although these results are corroborated by a parallel set of in vitro transfection experiments in aXenopuscell line, some key differences suggest the importance of using transgenic methods in conjunction with in vitro assays. Developmental Dynamics 230:229–238, 2004. © 2004 Wiley‐Liss, Inc.