Zelda Potentiates Morphogen Activity by Increasing Chromatin Accessibility
Zelda Potentiates Morphogen Activity by Increasing Chromatin Accessibility
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DOI：
10.1016/j.cub.2014.04.032
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发表时间：
2014-06-16
期刊：
影响因子：
9.2
通讯作者：
Rushlow, Christine A.
中科院分区：
文献类型：
--
作者：
Foo, Sun Melody;Sun, Yujia;Rushlow, Christine A.
合子基因组激活（ZGA）是胚胎细胞开始采取特定命运的主要基因组编程事件。在果蝇和斑马鱼中的实验已经揭示，ZGA依赖于转录因子，这些转录因子通过与基因调控序列的直接和特异性结合来提供对基因表达的大规模控制[1-5]。Zelda（Zld）在果蝇胚胎中起着这样的作用，它已被证明可以控制模式信号的作用[1，2];然而，这种作用的机制仍然很不清楚。最近的一个模型提出，Zld结合位点作为Dorsal（DI）激活的基因时空表达的定量调节因子，DI是形成背腹轴的形态原[6]。在这里，我们使用Brinker（brk）和短原肠胚形成（sog）的增强剂实验性地测试了该模型，这两者都被DI直接激活，但在不同的浓度阈值下[7-9]。与该模型一致，我们表明，Zld结合位点的数量和增强子活性的空间域之间存在明显的正相关性。同样，表达的时间可以提前或延迟。我们提出的证据表明，ZLD促进DI的监管DNA的结合，这是与染色质可及性增加。重要的是，染色质可及性的变化与Zld结合的变化强烈相关，但与DI无关。我们认为，基因组激活因子促进转录输入读出的能力是ZGA期间广泛转录诱导的关键。
Zygotic genome activation (ZGA) is a major genome programming event whereby the cells of the embryo begin to adopt specified fates. Experiments in Drosophila and zebrafish have revealed that ZGA depends on transcription factors that provide large-scale control of gene expression by direct and specific binding to gene regulatory sequences [1-5]. Zelda (Zld) plays such a role in the Drosophila embryo, where it has been shown to control the action of patterning signals [1, 2]; however, the mechanisms underlying this effect remain largely unclear. A recent model proposed that Zld binding sites act as quantitative regulators of the spatiotemporal expression of genes activated by Dorsal (DI), the morphogen that patterns the dorsoventral axis [6]. Here we tested this model experimentally, using enhancers of brinker (brk) and short gastrulation (sog), both of which are directly activated by DI, but at different concentration thresholds [7-9]. In agreement with the model, we show that there is a clear positive correlation between the number of Zld binding sites and the spatial domain of enhancer activity. Likewise, the timing of expression could be advanced or delayed. We present evidence that Zld facilitates binding of DI to regulatory DNA, and that this is associated with increased chromatin accessibility. Importantly, the change in chromatin accessibility is strongly correlated with the change in Zld binding, but not DI. We propose that the ability of genome activators to facilitate readout of transcriptional input is key to widespread transcriptional induction during ZGA.