PT - JOURNAL ARTICLE AU - Andreas Große-Berkenbusch AU - Johannes Hettich AU - Timo Kuhn AU - Natalia Fili AU - Alexander W. Cook AU - Yukti Hari-Gupta AU - Anja Palmer AU - Lisa Streit AU - Peter J.I. Ellis AU - Christopher P. Toseland AU - J. Christof M. Gebhardt TI - Myosin VI moves on nuclear actin filaments and supports long-range chromatin rearrangements AID - 10.1101/2020.04.03.023614 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.04.03.023614 4099 - http://biorxiv.org/content/early/2020/04/04/2020.04.03.023614.short 4100 - http://biorxiv.org/content/early/2020/04/04/2020.04.03.023614.full AB - Nuclear myosin VI (MVI) enhances RNA polymerase II – dependent transcription, but the molecular mechanism is unclear. We used live cell single molecule tracking to follow individual MVI molecules inside the nucleus and observed micrometer-long motion of the motor. Besides static chromatin interactions lasting for tens of seconds, ATPase-dependent directed motion occurred with a velocity of 2 µm/s. The movement was frequently interrupted by short periods of slow restricted diffusion and increased in frequency upon stimulation of transcription. Mutagenesis and perturbation experiments demonstrated that nuclear MVI motion is independent of dimerization and occurs on nuclear actin filaments, which we also observed by two-color imaging. Using chromosome paint to quantify distances between chromosomes, we found that MVI is required for transcription-dependent long-range chromatin rearrangements. Our measurements reveal a transcription-coupled function of MVI in the nucleus, where it actively undergoes directed movement along nuclear actin filaments. Motion is potentially mediated by cooperating monomeric motors and might assist in enhancing transcription by supporting long-range chromatin rearrangements.