Zambrowicz B P, Palmiter R D
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Biol Reprod. 1994 Jan;50(1):65-72. doi: 10.1095/biolreprod50.1.65.
To understand the spermatid-specific regulation of the protamine-1 (Prm-1) gene, we examined the nuclear proteins that bind to regions of the Prm-1 promoter known to regulate transcription. We focused on the Prm-1 promoter region between bp -224 and -37 because this region directs spermatid-specific expression of a heterologous reporter gene in transgenic mice and because regulatory function has been demonstrated for several subregions of this fragment. Testis nuclear proteins that bind to this promoter region were identified by means of gel mobility shift assays, and the tissue distribution of these proteins was examined through nuclear extracts derived from several mouse tissues. Nuclear extracts prepared from prepubertal and mutant mouse testes were used to demonstrate the developmental appearance of these DNA-binding proteins during spermatogenesis. These studies indicate that a testis-specific protein that appears after Day 12 interacts with a sequence (between bp -37 and -77) shown to be essential for Prm-1 transcription in vivo. In addition, a number of proteins that are not restricted to the testis interact with other functionally important regions of the Prm-1 promoter.
为了解鱼精蛋白-1(Prm-1)基因的精子细胞特异性调控,我们检测了与已知调控转录的Prm-1启动子区域结合的核蛋白。我们聚焦于-224至-37碱基对之间的Prm-1启动子区域,因为该区域在转基因小鼠中指导异源报告基因的精子细胞特异性表达,且该片段的几个亚区域已被证明具有调控功能。通过凝胶迁移率变动分析鉴定了与该启动子区域结合的睾丸核蛋白,并通过源自几种小鼠组织的核提取物检测了这些蛋白的组织分布。用青春期前和突变小鼠睾丸制备的核提取物来证明这些DNA结合蛋白在精子发生过程中的发育出现情况。这些研究表明,在第12天后出现的一种睾丸特异性蛋白与一个序列(-37至-77碱基对之间)相互作用,该序列在体内对Prm-1转录至关重要。此外,一些不限于睾丸的蛋白与Prm-1启动子的其他功能重要区域相互作用。