Gonzalez Federico, Duboule Denis, Spitz François
National Center for Competence in Research/Frontiers in Genetics, Department of Zoology and Animal Biology, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Dev Biol. 2007 Jun 15;306(2):847-59. doi: 10.1016/j.ydbio.2007.03.020. Epub 2007 Mar 23.
In tetrapods, posterior Hoxd genes (from groups 10 to 13) are necessary to properly pattern the developing autopods, including the number and identities of digits. Their coordinated expression is achieved by sharing a global control region (GCR), which was isolated and localized 200 kb 5' (centromeric) of the gene cluster. However, in transgenic assays, the GCR was unable to fully recapitulate all aspects of the endogenous Hoxd expression patterns during distal limb development. In this paper, we further analyze the regulatory potential of this locus and report the characterization of Prox, a second enhancer element that contributes to the transcriptional activity of posterior Hoxd genes in developing distal limb buds. We show that the GCR and Prox elements complement each other and work in combination to correctly establish the late phase of Hoxd genes expression. Based on DNA sequence conservation and transgenic assays, we discuss the functions of these regulatory regions as well as a potential evolutionary scheme accounting for their emergence along with the evolution of tetrapod limbs.
在四足动物中，后位Hoxd基因（第10至13组）对于正确构建发育中的手足，包括指（趾）的数量和特征，是必不可少的。它们的协调表达是通过共享一个全局控制区域（GCR）来实现的，该区域在基因簇的5'（着丝粒）端200 kb处被分离和定位。然而，在转基因实验中，GCR无法完全重现远端肢体发育过程中内源性Hoxd表达模式的所有方面。在本文中，我们进一步分析了该基因座的调控潜力，并报道了Prox的特征，Prox是第二个增强子元件，有助于后位Hoxd基因在发育中的远端肢体芽中的转录活性。我们表明，GCR和Prox元件相互补充，并共同作用以正确建立Hoxd基因表达的后期阶段。基于DNA序列保守性和转基因实验，我们讨论了这些调控区域的功能以及一个潜在的进化方案，该方案解释了它们随着四足动物肢体的进化而出现的原因。
