Sequence-specific transactivators counteract topoisomerase II-mediated inhibition ofin vitrotranscription by RNA polymerases I and II

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Abstract
An Inhibitor of RNA polymerase II transcription in vitro has been purified from HeLa cell nuclear extracts. Partial amlno acid sequences derived from the purified protein revealed that the inhibitor of transcription corresponded to human topoisomerase II. Order of addition experiments provided evidence Indicating that topoisomerase II inhibited transcription by binding over the core promoter and blocking prelnltiation complex formation. Topoisomerase ll-mediated repression could be relieved by sequence-specific transcriptional activators, having different activating and/or DNA binding domains, but antirepresslon required a transcriptional activation function in addition to a DNA binding domain. Moreover, transcription by RNA polymerase I was also inhibited by topoisomerase II and this inhibition could be relieved by the RNA polymerase I transactivator UBF. These observations suggest that topoisomerase II may participate in a general repression of transcription which can be counteracted by transcriptional activators.