Dual regulation and redundant function of two eye-specific enhancers of the Drosophila retinal determination gene dachshund
Dual regulation and redundant function of two eye-specific enhancers of the Drosophila retinal determination gene dachshund
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DOI：
10.1242/dev.01869
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发表时间：
2005-06-01
期刊：
影响因子：
4.6
通讯作者：
Mardon, G
中科院分区：
文献类型：
--
作者：
Pappu, KS;Ostrin, EJ;Mardon, G
果蝇的眼睛发育是由一个保守的视网膜决定基因网络控制的。RD基因编码核蛋白，形成复合体，与细胞外信号调节的转录因子协同发挥功能。识别控制RD基因眼睛特异性表达的基因组调控元件将使我们更好地理解基因表达在眼睛早期发育过程中的时空调控。我们比较了5种果蝇在RD基因Dachshund(DAC)40kb附近的保守非编码序列(CNCSs)。我们的分析发现，在DAC基因座的8号内含子和3‘非编码区中有两个独立的眼睛增强子，这些区域由高度保守的序列簇定义。功能丧失和功能获得分析表明，3‘增眼剂受eya、so和DPP信号的协同激活，仅被ey间接激活，而5’增眼剂主要受ey调节，与eya和so协同作用。破坏3‘眼睛增强剂中保守的SO结合位点可以阻止报告基因在体内的表达。我们的结果表明，这两种眼睛增强剂相互冗余和协同作用，整合了不同的上游输入，并指导了DAC的眼睛特异性表达。
Drosophila eye development is controlled by a conserved network of retinal determination (RD) genes. The RD genes encode nuclear proteins that form complexes and function in concert with extracellular signal-regulated transcription factors. Identification of the genomic regulatory elements that govern the eye-specific expression of the RD genes will allow us to better understand how spatial and temporal control of gene expression occurs during early eye development. We compared conserved non-coding sequences (CNCSs) between five Drosophilids along the similar to 40 kb genomic locus of the RD gene dachshund (dac). Our analysis uncovers two separate eye enhancers in intron eight and the 3' non-coding regions of the dac locus defined by clusters of highly conserved sequences. Loss- and gain-of-function analyses suggest that the 3' eye enhancer is synergistically activated by a combination of eya, so and dpp signaling, and only indirectly activated by ey, whereas the 5' eye enhancer is primarily regulated by ey, acting in concert with eya and so. Disrupting conserved So-binding sites in the 3' eye enhancer prevents reporter expression in vivo. Our results suggest that the two eye enhancers act redundantly and in concert with each other to integrate distinct upstream inputs and direct the eye-specific expression of dac.