Shadow enhancers foster robustness of Drosophila gastrulation.
Shadow enhancers foster robustness of Drosophila gastrulation.
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DOI：
10.1016/j.cub.2010.07.043
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发表时间：
2010-09-14
期刊：
影响因子：
9.2
通讯作者：
Levine, Michael
中科院分区：
文献类型：
--
作者：
Perry, Michael W.;Boettiger, Alistair N.;Bothma, Jacques P.;Levine, Michael
最近对果蝇进行的全基因组分析表明，关键的发育控制基因有时含有“影子”增强子。这些基因可能位于遥远的位置，包括邻近基因的内含子。尽管如此，它们产生的基因表达模式与更接近的初级增强子所产生的模式相同或相似。有人建议，阴影增强剂有助于培养基因表达的稳健性，以响应环境或遗传扰动。在这里，我们通过使用BAC重组工程和定量共聚焦成像方法的组合来关键地检验这一假说。有证据表明，蜗牛基因受位于邻近的Tim17b2基因座的远端阴影增强子的调控。Snail编码一种锌指转录因子，该转录因子与广泛的发育过程和癌症的上皮/间充质转化(EMT)有关。去除近端的初级增强子不会显著扰乱蜗牛的功能，包括抑制神经性基因和在正常发育温度下原肠形成腹沟。然而，在高温下，蜗牛的表达会零星地丧失，同时原肠分裂也会中断。在正常温度下，当蜗牛表达的关键激活物背侧水平降低时，也观察到类似的缺陷[回顾8]。总之，这些结果表明，阴影增强剂代表了一种新的管化机制，通过这种机制，复杂的发育过程“不管条件…的微小变化，都会产生一个明确的最终结果”。。
Recent whole-genome analyses in Drosophila suggest that critical developmental control genes sometimes contain “shadow” enhancers. These can be located in remote positions, including the introns of neighboring genes. They nonetheless produce patterns of gene expression that are the same or similar as 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. Here, we critically test this hypothesis by employing a combination of BAC recombineering and quantitative confocal imaging methods. Evidence is presented that the snail gene is regulated by a distal shadow enhancer located within the neighboring Tim17b2 locus. snail encodes a zinc finger transcription factor that has been implicated in epithelial/mesenchyme transitions (EMT) in a broad spectrum of developmental processes and cancers. 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 of development. 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 8]. Altogether, 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…”.
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影响因子：
64.8
作者：
通讯作者：
--
通过间隙基因交叉调节，基因表达在果蝇芽孢杆菌中进行了渠道化。
影响因子：
9.8
作者：
Manu;Surkova S;Spirov AV;Gursky VV;Janssens H;Kim AR;Radulescu O;Vanario-Alonso CE;Sharp DH;Samsonova M;Reinitz J
通讯作者：
Reinitz J
影响因子：
14.9
作者：
Warming S;Costantino N;Court DL;Jenkins NA;Copeland NG
通讯作者：
Copeland NG
DOI：
10.1073/pnas.0806476105
发表时间：
2008-12-23
影响因子：
11.1
作者：
Hong, Joung-Woo;Hendrix, David A.;Levine, Michael S.
通讯作者：
Levine, Michael S.
影响因子：
7
作者：
Kikuta, Hiroshi;Laplante, Mary;Becker, Thomas S.
通讯作者：
Becker, Thomas S.