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

Biology

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

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 (US)
Article number	1346
Pages (from-to)	1346
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28962-w
State	Published - Mar 15 2022

Keywords

Animals
Cell Nucleus/genetics
Mammals/genetics
Myosin Heavy Chains/genetics
RNA Polymerase II/genetics
Transcription, Genetic

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

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10.1038/s41467-022-28962-w

Cite this

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), 1346. Article 1346. https://doi.org/10.1038/s41467-022-28962-w

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, pp. 1346. https://doi.org/10.1038/s41467-022-28962-w

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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.",

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

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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 - 2022/3/15

Y1 - 2022/3/15

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.

KW - Animals

KW - Cell Nucleus/genetics

KW - Mammals/genetics

KW - Myosin Heavy Chains/genetics

KW - RNA Polymerase II/genetics

KW - Transcription, Genetic

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Myosin VI regulates the spatial organisation of mammalian transcription initiation

Abstract

Keywords

ASJC Scopus subject areas

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