Clyde Dorothy E, Corado Maria S G, Wu Xuelin, Paré Adam, Papatsenko Dmitri, Small Stephen
Biology Department, New York University, New York, New York 10003, USA.
Nature. 2003 Dec 18;426(6968):849-53. doi: 10.1038/nature02189.
Gradients of regulatory factors are essential for establishing precise patterns of gene expression during development; 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.
调控因子的梯度对于在发育过程中建立精确的基因表达模式至关重要；然而，目前尚不清楚多个梯度中的模式信息是如何整合以产生复杂的身体结构的。在这里，我们表明果蝇的两种转录抑制因子驼背（Hb）和克尼普斯（Kni）的相反梯度通过差异抑制成对规则基因偶数跳动（eve）的两个不同调控区域（增强子）来定位几个节段。计算分析和体内分析表明，增强子对抑制的敏感性由阻遏物结合位点的数量和亲和力控制。由于kni表达域位于Hb的两个梯度之间，每个增强子指导一对对称条纹的表达，在kni域的每一侧各有一条。因此，八个条纹边界（四条条纹）的精确定位，即整个eve模式的一半以上，仅需要两个增强子。我们的结果表明，简单的抑制因子梯度可以产生复杂的发育表达模式。它们还支持计算分析在定义和解读基因组DNA中包含的调控信息方面的实用性。
