The sea urchin endomesoderm gene regulatory network, an encoded logic map for early development

E. Davidson
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Abstract

The regulatory program for animal development is "wired" into the cis-regulatory networks of the genome. At the DNA level these networks consist of the clusters of cis-regulatory transcription factor target sites (modules) that direct the spatial and temporal expression of each phase of activity of those genes; and the linkages amongst them. Here "linkage" refers to the relation between genes encoding transcription factors and the target sites of genes which they control, and between the genes encoding elements of signal systems and their ultimate target genes. We are engaged in an effort to define at the genomic sequence level the gene regulatory network (GRN) controlling endomesoderm specification in sea urchin embryos. The proposed GRN is based on the following information: spatial and temporal expression patterns of all genes included; constraints from experimental embryology; and a massive perturbation analysis in which expression of every relevant gene is perturbed and the effects on all other genes measured. The GRN consists of predicted inputs into the cis-regulatory modules controlling the endomesoderm expression of the genes involved. These predictions can be tested at the cis-regulatory level: here several such tests are presented. They show that the perturbation analysis is a surprisingly informative predictor of DNA sequence-level regulatory transactions.
海胆内胚层基因调控网络,早期发育的编码逻辑图谱
动物发育的调控程序被“连接”到基因组的顺式调控网络中。在DNA水平上,这些网络由顺式调控转录因子靶位点(模块)组成,这些位点指导这些基因活性的每个阶段的空间和时间表达;以及它们之间的联系。这里的“连锁”是指编码转录因子的基因与其所控制基因的靶位点之间的关系,以及编码信号系统元件的基因与其最终靶基因之间的关系。我们致力于在基因组序列水平上定义控制海胆胚胎内胚层规范的基因调控网络(GRN)。所提出的GRN基于以下信息:所有基因的时空表达模式;实验胚胎学的限制;还有一个大规模的扰动分析,其中每个相关基因的表达都受到干扰,并测量对所有其他基因的影响。GRN包括对顺式调控模块的预测输入,该模块控制相关基因的内胚层表达。这些预测可以在顺式监管层面上得到检验:这里提出了几个这样的检验。他们表明,扰动分析是DNA序列水平调控交易的令人惊讶的信息预测器。
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