A self-organizing system of repressor gradients establishes segmental complexity in Drosophila
A self-organizing system of repressor gradients establishes segmental complexity in Drosophila
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DOI：
10.1038/nature02189
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发表时间：
2003-12-18
期刊：
影响因子：
64.8
通讯作者：
Small, S
中科院分区：
文献类型：
--
作者：
Clyde, DE;Corado, MSG;Small, S
调控因子的表达对于在发育过程中建立精确的基因表达模式至关重要（1-3）;然而，目前尚不清楚如何整合多个梯度中的模式信息以生成复杂的身体计划。在这里，我们表明，相反的梯度的两个果蝇转录抑制因子，驼背（Hb）和Knirps（Kni），通过差异抑制两个不同的调控区（增强子）的配对规则基因甚至跳过（前夕）的位置几个片段。计算和体内分析表明，增强子对阻遏的敏感性受阻遏物结合位点的数量和亲和力控制。因为kni表达结构域位于两个梯度的Hb之间，所以每个增强子指导一对对称条纹的表达，kni结构域的每一侧各一个。因此，仅需要两个增强器来精确定位八个条纹边界（四个条纹），或者超过整个eve图案的一半。我们的研究结果表明，复杂的发育表达模式可以产生简单的阻遏梯度。它们还支持用于定义和破译基因组DNA中包含的调控信息的计算分析的效用。
Gradients of regulatory factors are essential for establishing precise patterns of gene expression during development(1-3); however, it is not clear how patterning information in multiple gradients is integrated to generate complex body plans. Here we show that opposing gradients of two Drosophila transcriptional repressors, Hunchback (Hb) and Knirps (Kni), position several segments by differentially repressing two distinct regulatory regions (enhancers) of the pair-rule gene even-skipped (eve). Computational and in vivo analyses suggest that enhancer sensitivity to repression is controlled by the number and affinity of repressor-binding sites. Because the kni expression domain is positioned between two gradients of Hb, each enhancer directs expression of a pair of symmetrical stripes, one on each side of the kni domain. Thus, only two enhancers are required for the precise positioning of eight stripe borders (four stripes), or more than half of the whole eve pattern. Our results show that complex developmental expression patterns can be generated by simple repressor gradients. They also support the utility of computational analyses for defining and deciphering regulatory information contained in genomic DNA.