Appel B, Sakonju S
Department of Human Genetics, Howard Hughes Medical Institute, University of Utah, Salt Lake City 84112.
EMBO J. 1993 Mar;12(3):1099-109. doi: 10.1002/j.1460-2075.1993.tb05751.x.
The homeotic genes of Drosophila melanogaster, which are required for specification of segmental identities, encode proteins capable of regulating gene expression. We have chosen to study the organization and function of a regulatory target in an attempt to learn how homeotic gene products provide appropriate transcriptional controls. We identified 30 common binding sites for the proteins encoded by the Ultrabithorax (Ubx) and abdominal-A (abd-A) genes within a negatively regulated target, the P2 promoter of the Antennapedia (Antp) gene. By systematically mutagenizing binding sites and observing the resulting P2 expression pattern in embryos, we have found evidence for cell-type-specific interactions that are mediated by these sequences. In certain neuronal cells, UBX and ABD-A proteins appear to repress by competing for common binding sites with another homeodomain protein, which we propose to be ANTP acting to induce P2 transcription in an autoregulatory manner. In sets of cells that contribute to the tracheal system, UBX and ABD-A repress by counteracting the function of a factor acting at independent sites. The latter mechanism of repression requires only that multiple homeodomain binding sequences be present and is not dependent on any particular binding site.
黑腹果蝇的同源异型基因对于确定体节特征是必需的，它们编码能够调节基因表达的蛋白质。我们选择研究一个调控靶点的组织和功能，试图了解同源异型基因产物是如何提供适当的转录控制的。我们在一个负调控靶点——触角足（Antp）基因的P2启动子中，鉴定出了由超双胸（Ubx）和腹A（abd-A）基因编码的蛋白质的30个共同结合位点。通过系统地诱变结合位点并观察胚胎中由此产生的P2表达模式，我们发现了由这些序列介导的细胞类型特异性相互作用的证据。在某些神经元细胞中，UBX和ABD-A蛋白似乎通过与另一种同源结构域蛋白竞争共同结合位点来发挥抑制作用，我们认为这种同源结构域蛋白是触角足蛋白（ANTP），它以一种自调节方式诱导P2转录。在构成气管系统的细胞群中，UBX和ABD-A通过抵消作用于独立位点的一个因子的功能来发挥抑制作用。后一种抑制机制只要求存在多个同源结构域结合序列，并不依赖于任何特定的结合位点。
