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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Article number1346
Pages (from-to)1346
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - 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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