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Myosin VI moves on nuclear actin filaments and supports long-range chromatin rearrangements

Andreas Große-Berkenbusch, Johannes Hettich, Timo Kuhn, Natalia Fili, Alexander W. Cook, Yukti Hari-Gupta, Anja Palmer, Lisa Streit, Peter J.I. Ellis, Christopher P. Toseland, J. Christof M. Gebhardt
doi: https://doi.org/10.1101/2020.04.03.023614
Andreas Große-Berkenbusch
1Ulm University, Institute of Biophysics, Albert-Einstein-Allee 11, 89081 Ulm, Germany
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Johannes Hettich
1Ulm University, Institute of Biophysics, Albert-Einstein-Allee 11, 89081 Ulm, Germany
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Timo Kuhn
1Ulm University, Institute of Biophysics, Albert-Einstein-Allee 11, 89081 Ulm, Germany
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Natalia Fili
2University of Sheffield, Department of Oncology and Metabolism, The Medical School, Beech Hill Road, Sheffield, S10 2RX, UK
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Alexander W. Cook
2University of Sheffield, Department of Oncology and Metabolism, The Medical School, Beech Hill Road, Sheffield, S10 2RX, UK
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Yukti Hari-Gupta
3School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK
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Anja Palmer
1Ulm University, Institute of Biophysics, Albert-Einstein-Allee 11, 89081 Ulm, Germany
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Lisa Streit
1Ulm University, Institute of Biophysics, Albert-Einstein-Allee 11, 89081 Ulm, Germany
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Peter J.I. Ellis
3School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK
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Christopher P. Toseland
2University of Sheffield, Department of Oncology and Metabolism, The Medical School, Beech Hill Road, Sheffield, S10 2RX, UK
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  • For correspondence: c.toseland@sheffield.ac.uk christof.gebhardt@uni-ulm.de
J. Christof M. Gebhardt
1Ulm University, Institute of Biophysics, Albert-Einstein-Allee 11, 89081 Ulm, Germany
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  • For correspondence: c.toseland@sheffield.ac.uk christof.gebhardt@uni-ulm.de
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Abstract

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.

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Posted April 04, 2020.
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Myosin VI moves on nuclear actin filaments and supports long-range chromatin rearrangements
Andreas Große-Berkenbusch, Johannes Hettich, Timo Kuhn, Natalia Fili, Alexander W. Cook, Yukti Hari-Gupta, Anja Palmer, Lisa Streit, Peter J.I. Ellis, Christopher P. Toseland, J. Christof M. Gebhardt
bioRxiv 2020.04.03.023614; doi: https://doi.org/10.1101/2020.04.03.023614
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Myosin VI moves on nuclear actin filaments and supports long-range chromatin rearrangements
Andreas Große-Berkenbusch, Johannes Hettich, Timo Kuhn, Natalia Fili, Alexander W. Cook, Yukti Hari-Gupta, Anja Palmer, Lisa Streit, Peter J.I. Ellis, Christopher P. Toseland, J. Christof M. Gebhardt
bioRxiv 2020.04.03.023614; doi: https://doi.org/10.1101/2020.04.03.023614

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