Jiang J, Rushlow C A, Zhou Q, Small S, Levine M
Department of Biological Sciences, Fairchild Center, Columbia University, New York, NY 10027.
EMBO J. 1992 Aug;11(8):3147-54. doi: 10.1002/j.1460-2075.1992.tb05387.x.
The dorsal (dl) morphogen gradient is responsible for initiating the differentiation of the mesoderm, neuroectoderm and dorsal ectoderm in the Drosophila embryo. dl encodes a sequence-specific DNA binding protein that belongs to the Rel family of transcription factors. Previous studies have shown that dl activates the mesoderm determinant twist (twi); here we use a combination of site-directed mutagenesis and P-transformation assays to demonstrate that it also functions as a direct transcriptional repressor of a second target gene, zerknüllt (zen). By exchanging dl binding sites between the promoters we show that activator sites from twi can mediate repression when placed in the context of the zen promoter, and that repressor sites from zen can mediate activation in the context of the twi promoter. This represents the first demonstration that common binding sites for any DNA binding protein can mediate both activation and repression in a developing embryo. Evidence is also presented that the affinities of dl binding sites are important for the efficiency of repression, but are not the sole determinants of the threshold response to the dl gradient.
背侧（dl）形态发生素梯度负责启动果蝇胚胎中中胚层、神经外胚层和背侧外胚层的分化。dl编码一种序列特异性DNA结合蛋白，属于Rel转录因子家族。先前的研究表明，dl激活中胚层决定因子twist（twi）；在这里，我们使用定点诱变和P转化分析相结合的方法来证明它还作为第二个靶基因zerknüllt（zen）的直接转录抑制因子发挥作用。通过在启动子之间交换dl结合位点，我们表明来自twi的激活位点在置于zen启动子的背景下时可以介导抑制作用，而来自zen的抑制位点在twi启动子的背景下可以介导激活作用。这是首次证明任何DNA结合蛋白的共同结合位点在发育中的胚胎中都可以介导激活和抑制作用。还提供了证据表明，dl结合位点的亲和力对抑制效率很重要，但不是对dl梯度阈值反应的唯一决定因素。
