Papenbrock T, Peterson R L, Lee R S, Hsu T, Kuroiwa A, Awgulewitsch A
Department of Medicine, Medical University of South Carolina, Charleston 29425, USA.
Dev Dyn. 1998 Aug;212(4):540-7. doi: 10.1002/(SICI)1097-0177(199808)212:4<540::AID-AJA7>3.0.CO;2-H.
Reporter gene analysis of the Hoxc-9 genomic region in transgenic mice allowed us to identify a positional enhancer in the Hoxc-9 intron that drives expression in the posterior neural tube of midgestation mouse embryos in a Hoxc-9-related manner. Sequence comparison to the chicken Choxc-9 intron revealed the existence of two highly conserved sequence elements (CSEs) in a similar spatial arrangement. These structural similarities in the mammalian and avian lineage are mirrored by conserved function of the chicken Choxc-9 intron in transgenic mice. Deletion analysis of the two introns suggests that full activity of both enhancers depends on cooperation between the two CSEs located close to the respective 5' and 3' splice sites. Following the paradigm of phylogenetically conserved developmental control mechanisms, the Hoxc-9 intragenic enhancer was tested in Drosophila. Our data show that the mouse Hoxc-9 enhancer acts in a conserved fashion in transgenic flies, conferring posteriorly restricted reporter gene expression to the developing central nervous system in third instar larvae. This finding indicates that the Hoxc-9 intragenic enhancer is involved in transcriptional regulatory circuits conserved between vertebrates and arthropods.
对转基因小鼠中Hoxc-9基因组区域进行报告基因分析，使我们能够在Hoxc-9内含子中鉴定出一个位置增强子，该增强子以与Hoxc-9相关的方式驱动妊娠中期小鼠胚胎后神经管中的表达。与鸡Choxc-9内含子的序列比较揭示了两个高度保守的序列元件（CSE）以相似的空间排列存在。哺乳动物和鸟类谱系中的这些结构相似性反映在转基因小鼠中鸡Choxc-9内含子的保守功能上。对两个内含子的缺失分析表明，两个增强子的完全活性取决于位于各自5'和3'剪接位点附近的两个CSE之间的合作。按照系统发育保守的发育控制机制的范例，在果蝇中测试了Hoxc-9基因内增强子。我们的数据表明，小鼠Hoxc-9增强子在转基因果蝇中以保守的方式起作用，赋予第三龄幼虫发育中的中枢神经系统后部受限的报告基因表达。这一发现表明，Hoxc-9基因内增强子参与了脊椎动物和节肢动物之间保守的转录调控回路。
