Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, 606-8502, Japan.
Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, 606-8502, Japan.
Dev Biol. 2021 Aug;476:11-17. doi: 10.1016/j.ydbio.2021.03.010. Epub 2021 Mar 20.
In early embryos of Ciona, an invertebrate chordate, the animal-vegetal axis is established by the combinatorial actions of maternal factors. One target of these maternal factors, Foxd, is specifically expressed in the vegetal hemisphere and stabilizes the animal-vegetal axis by activating vegetal hemisphere-specific genes and repressing animal hemisphere-specific genes. This dual functionality is essential for the embryogenesis of early ascidian embryos; however, the mechanism by which Foxd can act as both a repressor and an activator is unknown. Here, we identify a Foxd binding site upstream of Lhx3/4, which is activated by Foxd, and compare it with a repressive Foxd binding site upstream of Dmrt.a. We found that activating sites bind Foxd with low affinity while repressive sites bind Foxd with high affinity. Reporter assays confirm that this qualitative difference between activating and repressive Foxd binding sites is sufficient to change Foxd functionality. We therefore conclude that the outcome of Foxd transcriptional regulation is encoded in cis-regulatory elements.
在无脊椎脊索动物海鞘的早期胚胎中，动物-植物轴是由母体因子的组合作用建立的。这些母体因子的一个靶标 Foxd 特异性地在植物半球中表达，并通过激活植物半球特异性基因和抑制动物半球特异性基因来稳定动物-植物轴。这种双重功能对于早期海鞘胚胎的胚胎发生是必不可少的；然而，Foxd 如何既能作为抑制剂又能作为激活剂发挥作用的机制尚不清楚。在这里，我们鉴定了 Lhx3/4 上游的一个 Foxd 结合位点，该位点被 Foxd 激活，并将其与 Dmrt.a 上游的抑制性 Foxd 结合位点进行比较。我们发现激活位点与 Foxd 结合的亲和力较低，而抑制性位点与 Foxd 结合的亲和力较高。报告基因实验证实，激活和抑制 Foxd 结合位点之间的这种定性差异足以改变 Foxd 的功能。因此，我们得出结论，Foxd 转录调控的结果是由顺式调控元件编码的。
