A Topoisomerase Ⅱβ-Mediated dsDNA Break Required for Regulated Transcription

摘要

Multiple enzymatic activities are required for transcriptional initiation. The enzyme DNA topoisomerase Ⅱ associates with gene promoter regions and can generate breaks in double-stranded DNA (dsDNA). Therefore, it is of interest to know whether this enzyme is critical for regulated gene activation. We report that the signal-dependent activation of gene transcription by nuclear receptors and other classes of DNA binding transcription factors, including activating protein 1, requires DNA topoisomerase Ⅱβ-dependent, transient, site-specific dsDNA break formation. Subsequent to the break, poly(adenosine diphosphate-ribose) polymerase-1 enzymatic activity is induced, which is required for a nudeosome-specific histone H1-high-mobility group B exchange event and for local changes of chromatin architecture. Our data mechanistically link DNA topoisomerase Ⅱβ-dependent dsDNA breaks and the components of the DNA damage and repair machinery in regulated gene transcription.