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.
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
UR - http://www.scopus.com/inward/record.url?scp=85126546582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126546582&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-28962-w
DO - 10.1038/s41467-022-28962-w
M3 - Article
C2 - 35292632
AN - SCOPUS:85126546582
VL - 13
SP - 1346
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1346
ER -