Horn G T, Wells R D
J Biol Chem. 1981 Feb 25;256(4):2003-9.
The effect of regions adjacent to the lambda PL promoter was studied using a sequence deleted in an A/T-rich segment immediately upstream from the promoter. High resolution thermal denaturation analysis showed that the undeleted sequence, as isolated on a 360-bp restriction fragment (360-PL) melted in two distinct steps. Since the deleted sequence (230-PL) melts at a higher temperature than any portion of 360-PL, the deleted promoter is more stable to denaturation. This increased stability was also suggested by a transcription assay in which the strong binding of RNA polymerase is inhibited at low temperature. The deleted promoter fragment required a higher temperature to become functional than did the 360-PL fragment. Furthermore, RNA polymerase bound to the 230-PL fragment is displaced by heparin at a faster rate than from 360-PL, and the deleted fragment initiates transcription at a reduced rate. Thus, by several criteria the deleted promoter is less active than the parent sequence. Evidence is presented arguing that the deletion does not alter the sequence directly recognized by RNA polymerase. Therefore, the altered sequence is reducing promoter activity by changing some other level of overall promoter structure. These results suggest that regions outside of the sequence directly recognized by a regulatory protein can affect genetic expression from the site.
利用在λPL启动子上游紧邻的富含A/T区域缺失的一段序列,研究了该区域的作用。高分辨率热变性分析表明,以360bp限制性片段(360-PL)形式分离得到的未缺失序列在两个不同步骤中解链。由于缺失序列(230-PL)在比360-PL的任何部分更高的温度下解链,所以缺失的启动子对变性更稳定。这一增加的稳定性也在转录试验中得到提示,在该试验中RNA聚合酶的强结合在低温下受到抑制。缺失的启动子片段比360-PL片段需要更高的温度才能发挥功能。此外,与230-PL片段结合的RNA聚合酶比与360-PL片段结合的RNA聚合酶更快地被肝素取代,并且缺失片段起始转录的速率降低。因此,从几个标准来看,缺失的启动子比亲本序列活性更低。有证据表明,该缺失并未直接改变RNA聚合酶直接识别的序列。因此,改变的序列通过改变整体启动子结构的某些其他水平来降低启动子活性。这些结果表明,调节蛋白直接识别的序列之外的区域可以影响该位点的基因表达。