Department of Integrative Biology, University of California-Berkeley, CA 94720, USA.
Curr Biol. 2010 Sep 14;20(17):1562-7. doi: 10.1016/j.cub.2010.07.043.
Critical developmental control genes sometimes contain "shadow" enhancers that can be located in remote positions, including the introns of neighboring genes [1]. They nonetheless produce patterns of gene expression that are the same as or similar to those produced by more proximal primary enhancers. It was suggested that shadow enhancers help foster robustness in gene expression in response to environmental or genetic perturbations [2, 3]. We critically tested this hypothesis by employing a combination of bacterial artificial chromosome (BAC) recombineering and quantitative confocal imaging methods [2, 4]. Evidence is presented that the snail gene is regulated by a distal shadow enhancer located within a neighboring locus. Removal of the proximal primary enhancer does not significantly perturb snail function, including the repression of neurogenic genes and formation of the ventral furrow during gastrulation at normal temperatures. However, at elevated temperatures, there is sporadic loss of snail expression and coincident disruptions in gastrulation. Similar defects are observed at normal temperatures upon reductions in the levels of Dorsal, a key activator of snail expression (reviewed in [5]). These results suggest that shadow enhancers represent a novel mechanism of canalization whereby complex developmental processes "bring about one definite end-result regardless of minor variations in conditions" [6].
关键发育调控基因有时包含“影子”增强子，这些增强子可以位于远程位置，包括邻近基因的内含子[1]。然而，它们产生的基因表达模式与更靠近的主要增强子产生的模式相同或相似。有人提出，影子增强子有助于增强基因表达对环境或遗传扰动的稳健性[2,3]。我们通过结合细菌人工染色体（BAC）重组和定量共聚焦成像方法[2,4]对这一假设进行了严格测试。有证据表明，蜗牛基因受位于邻近基因座内的远端影子增强子的调控。去除近端主要增强子不会显著扰乱蜗牛的功能，包括在正常温度下的原肠胚形成过程中对神经基因的抑制和腹沟的形成。然而，在高温下，蜗牛的表达会间歇性地丢失，同时原肠胚形成也会中断。在正常温度下， Dorsal 水平降低时也会观察到类似的缺陷， Dorsal 是蜗牛表达的关键激活剂（综述见[5]）。这些结果表明，影子增强子代表了一种新的 canalization 机制，通过该机制，复杂的发育过程“无论条件的微小变化如何，都会带来一个确定的最终结果”[6]。
