Conservation of enhancer location in divergent insects
Conservation of enhancer location in divergent insects
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DOI：
10.1073/pnas.0905754106
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发表时间：
2009-08-25
影响因子：
11.1
通讯作者：
Levine, Michael S.
中科院分区：
文献类型：
--
作者：
Cande, Jessica;Goltsev, Yury;Levine, Michael S.
果蝇胚胎的背腹侧（DV）模式由Dorsal的浓度梯度控制，Dorsal是一种与哺乳动物NF-κ B相关的序列特异性转录因子。Dorsal梯度通过对含有Dorsal、Twist、Snail和其他DV决定簇的结合位点的独特组合的靶增强子的差异调节产生至少3个不同的基因活性和组织特异性阈值。为了了解DV模式化机制的演变，我们从蚊子冈比亚按蚊和面粉甲虫赤拟谷盗中鉴定并表征了背靶增强子。假定的正向增强子位于相对于它们控制的靶基因的相似位置，即使它们缺乏序列保守性并且有时产生不同的基因表达模式。这种保守性最引人注目的例子是“阴影”增强子调节brinker：它在苍蝇和蚊子的相邻Atg 5基因座的内含子中是保守的。这些结果表明，像外显子，增强子的位置可能受到限制。因此，新的基因表达模式可能来自保守增强子的修饰，而不是新增强子的发明。我们建议，这种增强子的恒定性可能是一个普遍的属性的监管演变，并应促进增强子的发现在非模式生物。
Dorsoventral (DV) patterning of the Drosophila embryo is controlled by a concentration gradient of Dorsal, a sequence-specific transcription factor related to mammalian NF-kappa B. The Dorsal gradient generates at least 3 distinct thresholds of gene activity and tissue specification by the differential regulation of target enhancers containing distinctive combinations of binding sites for Dorsal, Twist, Snail, and other DV determinants. To understand the evolution of DV patterning mechanisms, we identified and characterized Dorsal target enhancers from the mosquito Anopheles gambiae and the flour beetle Tribolium castaneum. Putative orthologous enhancers are located in similar positions relative to the target genes they control, even though they lack sequence conservation and sometimes produce divergent patterns of gene expression. The most dramatic example of this conservation is seen for the "shadow'' enhancer regulating brinker: It is conserved within the intron of the neighboring Atg5 locus of both flies and mosquitoes. These results suggest that, like exons, an enhancer position might be subject to constraint. Thus, novel patterns of gene expression might arise from the modification of conserved enhancers rather than the invention of new ones. We propose that this enhancer constancy might be a general property of regulatory evolution, and should facilitate enhancer discovery in nonmodel organisms.