Computational models for neurogenic gene expression in the Drosophila embryo
Computational models for neurogenic gene expression in the Drosophila embryo
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DOI：
10.1016/j.cub.2006.05.044
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发表时间：
2006-07-11
期刊：
影响因子：
9.2
通讯作者：
Papatsenko, Dmitri
中科院分区：
文献类型：
--
作者：
Zinzen, Robert P.;Senger, Kate;Papatsenko, Dmitri
早期果蝇胚胎正在成为计算分析发育中基因调控的主要模型系统，因为控制分裂和原肠形成的大多数基因和许多相关的调控DNA都是已知的[1-5]。对果蝇基因网络的全面阐明提供了一个前所未有的机会，可以将定量模型应用于后生动物增强剂，这些增强剂在发育过程中控制基因表达的复杂模式[6-11]。基于确定的DNA结合位点占有率的模型已经被用来描述大肠杆菌中乳胶操纵子的调节和噬菌体lambda的裂解/溶源开关[12-15]。在这里，我们将类似的模型应用于果蝇早期胚胎腹侧神经源性外胚层(VNE)中受背侧梯度调节的增强子。基于背部、扭转和蜗牛结合位点占有率的定量模型提出了这样一种可能性，即这些调节蛋白之间的协同作用可能介导了vNE表达模式的细微差异。协同作用的差异可能归因于VNE增强子中背部、扭转和蜗牛结合位点的详细连接的不同。我们认为，结合位点占位是建立果蝇早期胚胎基因表达定位模式的关键限速步骤。
The early Drosophila embryo is emerging as a premiere model system for the computational analysis of gene regulation in development because most of the genes, and many of the associated regulatory DNAs, that control segmentation and gastrulation are known [1-5]. The comprehensive elucidation of Drosophila gene networks provides an unprecedented opportunity to apply quantitative models to metazoan enhancers that govern complex patterns of gene expression during development [6-11]. Models based on the fractional occupancy of defined DNA binding sites have been used to describe the regulation of the lac operon in E coli and the lysis/lysogeny switch of phage lambda [12-15]. Here, we apply similar models to enhancers regulated by the Dorsal gradient in the ventral neurogenic ectoderm (vNE) of the early Drosophila embryo. Quantitative models based on the fractional occupancy of Dorsal, Twist, and Snail binding sites raise the possibility that cooperative interactions among these regulatory proteins mediate subtle differences in the vNE expression patterns. Variations in co-operativity may be attributed to differences in the detailed linkage of Dorsal, Twist, and Snail binding sites in vNE enhancers. We propose that binding site occupancy is the key rate-limiting step for establishing localized patterns of gene expression in the early Drosophila embryo.