McKendry R, Harland R M, Stachel S E
Department of Molecular and Cell Biology, University of California at Berkeley, 401 Barker Hall, Berkeley, California, 94720, USA.
Dev Biol. 1998 Dec 1;204(1):172-86. doi: 10.1006/dbio.1998.9065.
Previous studies in both Xenopus and zebrafish have shown that goosecoid is one of the first genes to be transcribed at the onset of gastrulation. Goosecoid transcription still initiates when embryos are treated with protein synthesis inhibitors, indicating that it is mediated by preexisting factors and suggesting that goosecoid transcription is immediately downstream of the maternal mesoderm-inducing signal. However, goosecoid transcription continues long after this maternal signal has ceased to be active, indicating that there are mechanisms to maintain activin-induced transcription. Our study has focused on understanding the factors required to maintain this transcription. We have defined an element within the zebrafish goosecoid promoter that is sufficient for activin inducibility in both Xenopus and zebrafish embryos. This element, the goosecoid activin element, interacts with two developmentally regulated proteins from Xenopus embryos. A maternal protein interacts through cleavage stages until the midblastula transition, and a second protein binds from the onset of gastrulation. The second protein is zygotically expressed, and its binding is required for activin inducibility in our assay system. We suggest that the zygotic protein we have identified is a good candidate to be involved in the maintenance of goosecoid transcription. Furthermore, this zygotic protein is likely to contain a paired class homeodomain since a consensus binding site for such proteins is present within the goosecoid activin element and is essential for its function.
此前在非洲爪蟾和斑马鱼上开展的研究表明,鹅膏蕈氨酸是原肠胚形成开始时最早转录的基因之一。当胚胎用蛋白质合成抑制剂处理时,鹅膏蕈氨酸转录仍会启动,这表明它是由预先存在的因子介导的,也表明鹅膏蕈氨酸转录直接位于母体中胚层诱导信号的下游。然而,在这种母体信号停止活跃很久之后,鹅膏蕈氨酸转录仍在继续,这表明存在维持激活素诱导转录的机制。我们的研究重点是了解维持这种转录所需的因子。我们在斑马鱼鹅膏蕈氨酸启动子内确定了一个元件,该元件足以在非洲爪蟾和斑马鱼胚胎中实现激活素诱导。这个元件,即鹅膏蕈氨酸激活素元件,与来自非洲爪蟾胚胎的两种发育调控蛋白相互作用。一种母体蛋白在卵裂阶段一直相互作用,直到中囊胚转换,另一种蛋白从原肠胚形成开始就结合。第二种蛋白是合子表达的,在我们的检测系统中,其结合是激活素诱导所必需的。我们认为,我们鉴定出的合子蛋白很可能参与了鹅膏蕈氨酸转录的维持。此外,这种合子蛋白可能含有一个配对类同源结构域,因为在鹅膏蕈氨酸激活素元件内存在这种蛋白的共有结合位点,且该位点对其功能至关重要。