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

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/s41467-022-28962-w

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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), 1346. [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

@article{3b76c51b94874262aaf124592d3b6a18,

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.",

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

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 = "Funding Information: We thank the UKRI-MRC (MR/M020606/1), UKRI-STFC (19130001) and the Royal Society (IES\R3\183138) for funding to C.P.T. J.C.M.G. acknowledges funding by the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 Research and Innovation Program [637987 ChromArch] and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [422780363 SPP 2202 GE 2631/2-1]. Aberration-corrected multifocal microscopy was performed in collaboration with the Advanced Imaging Centre at Janelia Research Campus, a facility jointly supported by the Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation. We also thank Darren Griffin (University of Kent) and Alessia Buscaino (University of Kent) for sharing of equipment, and Satya Khuon (Janelia Research Campus) for assisting with cell culture. The JF549 dyes were kindly provided by Luke Lavis (Janelia Research Campus). We also thank grant from NYU Abu Dhabi, The Swedish Research Council and Cancerfonden to P.P. and we acknowledge technical help from the NYU Abu Dhabi Centre for Genomics and Sy`stems Biology, in particular Marc Arnoux and Mehar Sultana. We appreciate the computational platform provided by NYUAD HPC team and are especially thankful to Nizar Drou for technical help. Funding Information: We thank the UKRI-MRC (MR/M020606/1), UKRI-STFC (19130001) and the Royal Society (IES\R3\183138) for funding to C.P.T. J.C.M.G. acknowledges funding by the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 Research and Innovation Program [637987 ChromArch] and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [422780363 SPP 2202 GE 2631/2-1]. Aberration-corrected multifocal microscopy was performed in collaboration with the Advanced Imaging Centre at Janelia Research Campus, a facility jointly supported by the Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation. We also thank Darren Griffin (University of Kent) and Alessia Buscaino (University of Kent) for sharing of equipment, and Satya Khuon (Janelia Research Campus) for assisting with cell culture. The JF549 dyes were kindly provided by Luke Lavis (Janelia Research Campus). We also thank grant from NYU Abu Dhabi, The Swedish Research Council and Cancerfonden to P.P. and we acknowledge technical help from the NYU Abu Dhabi Centre for Genomics and Sy`stems Biology, in particular Marc Arnoux and Mehar Sultana. We appreciate the computational platform provided by NYUAD HPC team and are especially thankful to Nizar Drou for technical help. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = mar,

day = "15",

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

language = "English (US)",

volume = "13",

pages = "1346",

journal = "Nature Communications",

issn = "2041-1723",

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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.

N1 - Funding Information: We thank the UKRI-MRC (MR/M020606/1), UKRI-STFC (19130001) and the Royal Society (IES\R3\183138) for funding to C.P.T. J.C.M.G. acknowledges funding by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program [637987 ChromArch] and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [422780363 SPP 2202 GE 2631/2-1]. Aberration-corrected multifocal microscopy was performed in collaboration with the Advanced Imaging Centre at Janelia Research Campus, a facility jointly supported by the Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation. We also thank Darren Griffin (University of Kent) and Alessia Buscaino (University of Kent) for sharing of equipment, and Satya Khuon (Janelia Research Campus) for assisting with cell culture. The JF549 dyes were kindly provided by Luke Lavis (Janelia Research Campus). We also thank grant from NYU Abu Dhabi, The Swedish Research Council and Cancerfonden to P.P. and we acknowledge technical help from the NYU Abu Dhabi Centre for Genomics and Sy`stems Biology, in particular Marc Arnoux and Mehar Sultana. We appreciate the computational platform provided by NYUAD HPC team and are especially thankful to Nizar Drou for technical help. Funding Information: We thank the UKRI-MRC (MR/M020606/1), UKRI-STFC (19130001) and the Royal Society (IES\R3\183138) for funding to C.P.T. J.C.M.G. acknowledges funding by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program [637987 ChromArch] and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [422780363 SPP 2202 GE 2631/2-1]. Aberration-corrected multifocal microscopy was performed in collaboration with the Advanced Imaging Centre at Janelia Research Campus, a facility jointly supported by the Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation. We also thank Darren Griffin (University of Kent) and Alessia Buscaino (University of Kent) for sharing of equipment, and Satya Khuon (Janelia Research Campus) for assisting with cell culture. The JF549 dyes were kindly provided by Luke Lavis (Janelia Research Campus). We also thank grant from NYU Abu Dhabi, The Swedish Research Council and Cancerfonden to P.P. and we acknowledge technical help from the NYU Abu Dhabi Centre for Genomics and Sy`stems Biology, in particular Marc Arnoux and Mehar Sultana. We appreciate the computational platform provided by NYUAD HPC team and are especially thankful to Nizar Drou for technical help. Publisher Copyright: © 2022, The Author(s).

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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JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

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ER -

Myosin VI regulates the spatial organisation of mammalian transcription initiation

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Keywords

ASJC Scopus subject areas

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