Transcription-dependent dynamic supercoiling is a short-range genomic force

Transcription has the capacity to mechanically modify DNA topology, DNA structure and nucleosome arrangement. Resulting from ongoing transcription, these modifications in turn may provide instant feedback to the transcription machinery. To substantiate the connection between transcription and DNA dynamics, we charted an ENCODE map of transcription-dependent dynamic supercoiling in human Burkitt's lymphoma cells by using psoralen photobinding to probe DNA topology in vivo. Dynamic supercoils spread ~1.5 kilobases upstream of the start sites of active genes. Low- and high-output promoters handled this torsional stress differently, as shown by using inhibitors of transcription and topoisomerases and by chromatin immunoprecipation of RNA polymerase and topoisomerases I and II. Whereas lower outputs are managed adequately by topoisomerase I, high-output promoters additionally require topoisomerase II. The genome-wide coupling between transcription and DNA topology emphasizes the importance of dynamic supercoiling for gene regulation.