Wolf D A, Strobl L J, Pullner A, Eick D
Institut für Klinische Molekularbiologie und Tumorgenetik, Forschungszentrum für Umwelt und Gesundheit, GSF, München, Germany.
Nucleic Acids Res. 1995 Sep 11;23(17):3373-9. doi: 10.1093/nar/23.17.3373.
Transcriptional activation of the c-myc proto-oncogene is mediated by the transition of promoter proximal, paused RNA polymerase II (pol II) into a processive transcription mode. Using a transcription assay which allows the high resolution mapping of transcriptional complexes in intact nuclei, we have characterized the promoter proximal pause positions of pol II. Pol II paused in a nucleosome-free region close to the transcription start site as well as further downstream, between positions +17 and +52. These pause positions were detected in both transcriptionally active and inactive c-myc genes. Pharmacological inhibition of the C-terminal phosphorylation of the large subunit of pol II did not affect the paused transcription complexes, but had an inhibitory effect on transcription of nucleosomal DNA downstream of position +150. The different properties of pol II proximal and distal to the promoter suggest a model in which c-myc transcription is regulated by the activation of promoter bound polymerases.
原癌基因c-myc的转录激活是由启动子近端暂停的RNA聚合酶II(pol II)转变为持续转录模式介导的。我们使用一种转录分析方法,该方法可以对完整细胞核中的转录复合物进行高分辨率定位,从而确定了pol II在启动子近端的暂停位置。pol II在靠近转录起始位点以及更下游的无核小体区域暂停,位于+17至+52位点之间。在转录活性和非活性的c-myc基因中均检测到了这些暂停位置。对pol II大亚基C端磷酸化的药理学抑制并不影响暂停的转录复合物,但对+150位点下游核小体DNA的转录具有抑制作用。启动子近端和远端的pol II具有不同特性,这提示了一种模型,即c-myc转录是由与启动子结合的聚合酶的激活来调控的。