A Maternal System Initiating the Zygotic Developmental Program through Combinatorial Repression in the Ascidian Embryo.
A Maternal System Initiating the Zygotic Developmental Program through Combinatorial Repression in the Ascidian Embryo.
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DOI：
10.1371/journal.pgen.1006045
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发表时间：
2016-05
期刊：
影响因子：
4.5
通讯作者：
Satou Y
中科院分区：
文献类型：
--
作者：
Oda-Ishii I;Kubo A;Kari W;Suzuki N;Rothbächer U;Satou Y
母体因素启动动物胚胎的合子发育程序。在脊索动物玻璃海鞘的胚胎中，需要三种母体因子-Gata. a、β-catenin和Zic-r. a-来在16细胞期建立三个基因表达域：动物半球、植物半球和后植物区域。在这里，我们展示了母性因素如何建立这些领域。首先，仅β-连环蛋白及其效应转录因子Tcf 7需要建立植物半球结构域。其次，在后植物结构域特异性表达的基因具有额外的抑制性顺式元件，其拮抗β-连环蛋白/Tcf 7的活性。这种拮抗活性被Zic-r. a抑制，Zic-r. a特异性地定位于后植物结构域中，并通过与Tcf 7的相互作用间接地与DNA结合。第三，Gata. a指导动物半球结构域中的特异性基因表达，因为β-连环蛋白/Tcf 7通过植物细胞中的物理相互作用削弱了加塔. a对靶位点的结合活性。因此，抑制性调控通过蛋白质-蛋白质之间的相互作用的母体转录因子是必不可少的，以建立第一个不同的领域的基因表达的脊索动物胚胎。在动物发育过程中，转录因子和信号分子相互调控，构成了基因调控网络。这个网络是由母亲提供的因素引起的。许多母体因素都是局部的，从而激活特定区域的一组基因。在脊索动物玻璃海鞘的胚胎中，已知有三种具有局部活性的母体因子。本研究表明，这些本地化的母亲的因素相互作用，通过第四个非本地化的转录因子，Tcf 7，并负调节彼此。这些抑制性相互作用对于建立基因表达的第一个不同结构域和正确地唤起基因调控网络至关重要。这些发现表明，不仅激活靶基因，而且通过蛋白质-蛋白质相互作用抑制其他转录因子的活性对于正确启动合子程序是重要的。有趣的是，在一种抑制性相互作用中，转录因子通过与另一种转录因子的相互作用而失去其对靶位点的结合活性。因此，这项研究提供了一个完整的系统，其中母性因素启动的玻璃海鞘胚胎合子发育程序的描述。
Maternal factors initiate the zygotic developmental program in animal embryos. In embryos of the chordate, Ciona intestinalis, three maternal factors—Gata.a, β-catenin, and Zic-r.a—are required to establish three domains of gene expression at the 16-cell stage; the animal hemisphere, vegetal hemisphere, and posterior vegetal domains. Here, we show how the maternal factors establish these domains. First, only β-catenin and its effector transcription factor, Tcf7, are required to establish the vegetal hemisphere domain. Second, genes specifically expressed in the posterior vegetal domain have additional repressive cis-elements that antagonize the activity of β-catenin/Tcf7. This antagonizing activity is suppressed by Zic-r.a, which is specifically localized in the posterior vegetal domain and binds to DNA indirectly through the interaction with Tcf7. Third, Gata.a directs specific gene expression in the animal hemisphere domain, because β-catenin/Tcf7 weakens the Gata.a-binding activity for target sites through a physical interaction in the vegetal cells. Thus, repressive regulation through protein-protein interactions among the maternal transcription factors is essential to establish the first distinct domains of gene expression in the chordate embryo. During animal development, transcription factors and signaling molecules transcriptionally regulate one another and constitute a gene regulatory network. This network is evoked by maternally provided factors. Many maternal factors are localized and thereby activate a set of genes in a specific region. In embryos of the chordate, Ciona intestinalis, three maternal factors with localized activities are known. The present study demonstrated that these localized maternal factors interact with one another through a fourth non-localized transcription factor, Tcf7, and negatively regulate one another. These repressive interactions are essential to establish the first distinct domains of gene expression and evoke the gene regulatory network properly. The findings indicate that not only activating target genes but also repressing activities of other transcription factors through protein-protein interactions are important to properly initiate the zygotic program. Intriguingly, in one repressive interaction, a transcription factor loses its binding activity for target sites through an interaction with another transcription factor. Thus, this study provides a description of the entire system in which maternal factors initiate the zygotic developmental program of the Ciona embryo.