Variable pause positions of RNA polymerase II lie proximal to the c-myc promoter irrespective of transcriptional activity.
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.
Wolf
D A
DA
Institut für Klinische Molekularbiologie und Tumorgenetik, Forschungszentrum für Umwelt und Gesundheit, GSF, München, Germany.
Strobl
L J
LJ
Pullner
A
A
Eick
D
D
D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016259:Genes, myc; D018922:HL-60 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000648:ultrastructure; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D004791:Enzyme Inhibitors; C000715470:MAS1 protein, human; D009707:Nucleosomes; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D004004:Dichlororibofuranosylbenzimidazole; D012319:RNA Polymerase II