Kondo T, Zákány J, Duboule D
Department of Zoology and Animal Biology, University of Geneva, Switzerland.
Mol Cell. 1998 Jan;1(2):289-300. doi: 10.1016/s1097-2765(00)80029-5.
During development, vertebrate Hox genes are activated in a temporal and spatial sequence colinear with the position of the genes within their clusters. To investigate the mechanistic basis of this phenomenon, we used the ES cell technology and the loxP/Cre system to engineer a conditional fusion of the 5' exon of Hoxd-13 with the 3' exon of Hoxd-12. This hybrid transcription unit was regulated like Hoxd-11, with expression limits in the trunk, limbs, intestinal, and urogenital systems more anterior than those expected for either Hoxd-13 or Hoxd-12. An in vivo interspecies replacement by the fish homologous DNA fragment showed that anteriorization was not due to a distance effect, thus suggesting the presence of a regulatory element between Hoxd-13 and Hoxd-12 that may contribute to the establishment, early on, of a repressive state over these two genes.
在发育过程中，脊椎动物的Hox基因按时间和空间顺序被激活，这种顺序与其在基因簇中的位置共线。为了研究这一现象的机制基础，我们利用胚胎干细胞技术和loxP/Cre系统构建了一个条件性融合体，将Hoxd-13的5'外显子与Hoxd-12的3'外显子融合。这个杂交转录单元的调控方式与Hoxd-11类似，在躯干、四肢、肠道和泌尿生殖系统中的表达界限比Hoxd-13或Hoxd-12预期的更靠前。用鱼类同源DNA片段进行的体内种间替换表明，这种前移并非由距离效应引起，因此表明在Hoxd-13和Hoxd-12之间存在一个调控元件，它可能在早期就有助于对这两个基因建立抑制状态。
