Myosin VI regulates the spatial organisation of mammalian transcription initiation

Yukti Hari-Gupta, Natalia Fili, Ália dos Santos, Alexander W. Cook, Rosemarie E. Gough, Hannah C. W. Reed, Lin Wang, Jesse Aaron, Tomas Venit, Eric Wait, Andreas Grosse-Berkenbusch, J. Christof M. Gebhardt, Piergiorgio Percipalle, Teng-Leong Chew, Marisa Martin-Fernandez and Christopher P. Toseland ()
Additional contact information
Yukti Hari-Gupta: University of Kent
Natalia Fili: University of Sheffield
Ália dos Santos: University of Sheffield
Alexander W. Cook: University of Sheffield
Rosemarie E. Gough: University of Sheffield
Hannah C. W. Reed: University of Kent
Lin Wang: Rutherford Appleton Laboratory, Harwell, Didcot
Jesse Aaron: HHMI Janelia Research Campus
Tomas Venit: New York University Abu Dhabi (NYUAD)
Eric Wait: HHMI Janelia Research Campus
Andreas Grosse-Berkenbusch: Ulm University
J. Christof M. Gebhardt: Ulm University
Piergiorgio Percipalle: New York University Abu Dhabi (NYUAD)
Teng-Leong Chew: HHMI Janelia Research Campus
Marisa Martin-Fernandez: Rutherford Appleton Laboratory, Harwell, Didcot
Christopher P. Toseland: University of Sheffield

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract During transcription, RNA Polymerase II (RNAPII) is spatially organised within the nucleus into clusters that correlate with transcription activity. While this is a hallmark of genome regulation in mammalian cells, the mechanisms concerning the assembly, organisation and stability remain unknown. Here, we have used combination of single molecule imaging and genomic approaches to explore the role of nuclear myosin VI (MVI) in the nanoscale organisation of RNAPII. We reveal that MVI in the nucleus acts as the molecular anchor that holds RNAPII in high density clusters. Perturbation of MVI leads to the disruption of RNAPII localisation, chromatin organisation and subsequently a decrease in gene expression. Overall, we uncover the fundamental role of MVI in the spatial regulation of gene expression.

Date: 2022
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DOI: 10.1038/s41467-022-28962-w

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