Nolte Christof, Amores Angel, Nagy Kovács Erzsébet, Postlethwait John, Featherstone Mark
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Mech Dev. 2003 Mar;120(3):325-35. doi: 10.1016/s0925-4773(02)00442-2.
The zebrafish hoxd4a locus was compared to its murine ortholog, Hoxd4. The sequence of regulatory elements, including a DR5 type retinoic acid response element (RARE) required for Hoxd4 neural enhancer activity, are highly conserved. Additionally, zebrafish and mouse neural enhancers function identically in transgenic mouse embryos. We tested whether sequence conservation reflects functional importance by altering the spacing and sequence of the RARE in the Hoxd4 neural enhancer. Stabilizing receptor-DNA interactions did not anteriorize transgene expression. By contrast, conversion of the RARE from a DR5 to a DR2 type element decreased receptor-DNA stability and posteriorized expression. Hence, the setting of the Hox anterior expression border is not a simple function of the affinity of retinoid receptors for their cognate element.
将斑马鱼的hoxd4a基因座与其小鼠同源基因Hoxd4进行了比较。包括Hoxd4神经增强子活性所需的DR5型视黄酸反应元件（RARE）在内的调控元件序列高度保守。此外，斑马鱼和小鼠的神经增强子在转基因小鼠胚胎中的功能相同。我们通过改变Hoxd4神经增强子中RARE的间距和序列，测试了序列保守性是否反映功能重要性。稳定受体与DNA的相互作用并未使转基因表达向前移位。相比之下，将RARE从DR5型元件转换为DR2型元件会降低受体与DNA的稳定性，并使表达向后移位。因此，Hox基因前部表达边界的设定并非视黄酸受体与其同源元件亲和力的简单函数。
