Kirov N, Childs S, O'Connor M, Rushlow C
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
Mol Cell Biol. 1994 Jan;14(1):713-22. doi: 10.1128/mcb.14.1.713-722.1994.
The dorsal protein (DL) regulates the transcriptional activity of several genes that determine cell fate along the dorsoventral axis of the Drosophila melanogaster embryo. DL is present at high levels in ventral nuclei, where it activates some genes (twi and sna) and represses others (zen, dpp, and tld). DL shows homology to the Rel family of proteins and interacts with specific DNA sequences in the regulatory regions of its target genes. The distal portion of the zen gene acts as a silencer that can mediate the repression of a heterologous promoter in ventral regions of the embryo. It contains four DL binding sites which alone are sufficient for activation but not repression. Here we analyze the interaction of DL with another one of its repressed targets, the tolloid (tld) gene. Approximately 800 bp of 5'-flanking sequences upstream of the tld coding region were shown to drive an expression pattern indistinguishable from the wild-type pattern. A 423-bp fragment located within these sequences contains two DL binding sites and was shown to act as a silencer to mediate ventral repression. Point mutations in the sites abolish not only DNA binding but also ventral repression. We discuss a comparison of the DNA sequences from the zen and tld promoters and the possible mechanisms of transcriptional silencing.
背侧蛋白（DL）调节多个基因的转录活性，这些基因决定了黑腹果蝇胚胎背腹轴上的细胞命运。DL在腹侧细胞核中含量很高，在那里它激活一些基因（twi和sna）并抑制其他基因（zen、dpp和tld）。DL与Rel家族蛋白具有同源性，并与其靶基因调控区域中的特定DNA序列相互作用。zen基因的远端部分作为一个沉默子，可以介导胚胎腹侧区域中异源启动子的抑制。它包含四个DL结合位点，这些位点单独足以激活但不足以抑制。在这里，我们分析了DL与其另一个被抑制的靶标——类Toll蛋白（tld）基因之间的相互作用。tld编码区上游约800 bp的5'侧翼序列显示出与野生型模式无法区分的表达模式。位于这些序列内的一个423 bp片段包含两个DL结合位点，并被证明作为一个沉默子介导腹侧抑制。这些位点的点突变不仅消除了DNA结合，也消除了腹侧抑制。我们讨论了zen和tld启动子DNA序列的比较以及转录沉默的可能机制。
