Garg L C, Dixit A, Jacob S T
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033.
J Biol Chem. 1989 Jan 5;264(1):220-4.
Previous studies in this laboratory have demonstrated that a 174-base pair (bp) rat rDNA spacer region located more than 2 kilobase pairs upstream of the initiation site, can enhance rat rDNA transcription in vitro independent of its orientation or distance or when inserted downstream of the initiation site. Further dissection of this region showed that transcription of a rDNA fragment containing just 37 bp of the spacer sequence, located between -2.183 and -2.219 kilobase pairs upstream of the initiation site, is 8-fold greater than that of the rDNA fragment devoid of the spacer element. Electrophoretic mobility shift assay demonstrated specific interaction of the 37-bp DNA fragment with a cellular protein(s). The spacer DNA competed for essential transcription factors as demonstrated by the absence of transcription following preincubation of the extract with the 37-bp fragment. Similar competition was also observed when a 58-bp PolI promoter was substituted for the enhancer fragment. The binding of the factor(s) to the enhancer element was not altered when coding and noncoding strands of the 37-bp oligodeoxynucleotide were used separately in the competition assay. Since the 37-bp enhancer region and the core promoter do not exhibit any significant sequence homology, the factor(s) appears to interact with these cis-acting elements in a sequence-independent manner.
本实验室先前的研究表明,位于起始位点上游超过2千碱基对处的一段174碱基对(bp)的大鼠核糖体DNA间隔区,在体外可增强大鼠核糖体DNA转录,无论其方向或距离如何,或者当插入起始位点下游时也是如此。对该区域的进一步剖析表明,一个包含间隔序列仅37bp的核糖体DNA片段的转录,该片段位于起始位点上游-2.183至-2.219千碱基对之间,比不含间隔元件的核糖体DNA片段的转录高8倍。电泳迁移率变动分析表明37bp的DNA片段与一种细胞蛋白存在特异性相互作用。间隔DNA与必需转录因子竞争,这一点可通过提取物与37bp片段预孵育后转录缺失得到证明。当用58bp的RNA聚合酶I启动子替代增强子片段时,也观察到了类似的竞争。在竞争分析中分别使用37bp寡脱氧核苷酸的编码链和非编码链时,该因子与增强子元件的结合未发生改变。由于37bp的增强子区域与核心启动子未表现出任何显著的序列同源性,该因子似乎以不依赖序列的方式与这些顺式作用元件相互作用。