Jiménez G, Pinchin S M, Ish-Horowicz D
Imperial Cancer Research Fund, London, UK.
EMBO J. 1996 Dec 16;15(24):7088-98.
The Hairy and Runt pair-rule proteins regulate Drosophila segmentation by repressing transcription. To explore the ability of these proteins to function as promoter-bound regulators in vivo, we examined the effects of Hairy and Runt derivatives containing heterologous transcriptional activation domains (HairyAct and RunAct). Using this approach, we find that Hairy and Runt efficiently target such activation domains to specific segmentation gene promoters, leading to rapid induction of transcription. Our results strongly suggest that Hairy normally acts as a promoter-bound repressor of fushi tarazu, runt and odd-skipped, and that Runt directly represses even-skipped. We also show that expressing HairyAct in early blastoderm embryos causes ectopic Sex-lethal expression and male-specific lethality, implying that the Hairy-related denominator element Deadpan represses Sex-lethal during sex determination by directly recognizing the early Sex-lethal promoter.
毛状蛋白和矮胖蛋白通过抑制转录来调控果蝇的体节形成。为了探究这些蛋白在体内作为结合启动子的调节因子的功能,我们检测了含有异源转录激活结构域的毛状蛋白和矮胖蛋白衍生物(毛状激活蛋白和矮胖激活蛋白)的作用。通过这种方法,我们发现毛状蛋白和矮胖蛋白能有效地将此类激活结构域靶向特定的体节基因启动子,从而迅速诱导转录。我们的结果有力地表明,毛状蛋白通常作为腹肢、矮胖和奇跳基因启动子结合的阻遏物发挥作用,而矮胖蛋白直接抑制偶数跳基因。我们还表明,在早期囊胚胚胎中表达毛状激活蛋白会导致异位的性致死基因表达和雄性特异性致死,这意味着在性别决定过程中,与毛状蛋白相关的共同分母元件呆板蛋白通过直接识别早期性致死基因启动子来抑制性致死基因。