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; Christopher P. Toseland

doi:10.1038/s41467-022-28962-w

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
, Christopher P. Toseland

New York University Abu Dhabi

University of Kent
University College London
University of Sheffield
University of Lincoln
Rutherford Appleton Laboratory
Howard Hughes Medical Institute
Ulm University
Stockholm University

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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.

Original language	English
Article number	1346
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28962-w
State	Published - Dec 2022

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Hari-Gupta, Y., Fili, N., dos Santos, Á., Cook, A. W., Gough, R. E., Reed, H. C. W., Wang, L., Aaron, J., Venit, T., Wait, E., Grosse-Berkenbusch, A., Gebhardt, J. C. M., Percipalle, P., Chew, T. L., Martin-Fernandez, M., & Toseland, C. P. (2022). Myosin VI regulates the spatial organisation of mammalian transcription initiation. Nature Communications, 13(1), Article 1346. https://doi.org/10.1038/s41467-022-28962-w

@article{446b1b781aec4b438ea2baf3c7600187,

title = "Myosin VI regulates the spatial organisation of mammalian transcription initiation",

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.",

author = "Yukti Hari-Gupta and Natalia Fili and \{dos Santos\}, {\'A}lia and Cook, \{Alexander W.\} and Gough, \{Rosemarie E.\} and Reed, \{Hannah C.W.\} and Lin Wang and Jesse Aaron and Tomas Venit and Eric Wait and Andreas Grosse-Berkenbusch and Gebhardt, \{J. Christof M.\} and Piergiorgio Percipalle and Chew, \{Teng Leong\} and Marisa Martin-Fernandez and Toseland, \{Christopher P.\}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-28962-w",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

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Hari-Gupta, Y, Fili, N, dos Santos, Á, Cook, AW, Gough, RE, Reed, HCW, Wang, L, Aaron, J, Venit, T, Wait, E, Grosse-Berkenbusch, A, Gebhardt, JCM, Percipalle, P, Chew, TL, Martin-Fernandez, M & Toseland, CP 2022, 'Myosin VI regulates the spatial organisation of mammalian transcription initiation', Nature Communications, vol. 13, no. 1, 1346. https://doi.org/10.1038/s41467-022-28962-w

TY - JOUR

T1 - Myosin VI regulates the spatial organisation of mammalian transcription initiation

AU - Hari-Gupta, Yukti

AU - Fili, Natalia

AU - dos Santos, Ália

AU - Cook, Alexander W.

AU - Gough, Rosemarie E.

AU - Reed, Hannah C.W.

AU - Wang, Lin

AU - Aaron, Jesse

AU - Venit, Tomas

AU - Wait, Eric

AU - Grosse-Berkenbusch, Andreas

AU - Gebhardt, J. Christof M.

AU - Percipalle, Piergiorgio

AU - Chew, Teng Leong

AU - Martin-Fernandez, Marisa

AU - Toseland, Christopher P.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85126546582

U2 - 10.1038/s41467-022-28962-w

DO - 10.1038/s41467-022-28962-w

M3 - Article

C2 - 35292632

AN - SCOPUS:85126546582

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1346

ER -

Myosin VI regulates the spatial organisation of mammalian transcription initiation

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