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 - 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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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
SN - 2041-1723
VL - 13
SP - 1346
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1346
ER -