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Myosin VI regulates the spatial organisation of mammalian transcription initiation.

Yukti Hari-GuptaNatalia FiliÁlia Dos SantosAlexander W CookRosemarie E GoughHannah C W ReedLin WangJesse Scott AaronTomas VenitEric WaitAndreas Grosse-BerkenbuschJ Christof M GebhardtPiergiorgio PercipalleTeng-Leong ChewMarisa L Martin-FernandezChristopher P Toseland
Published in: Nature communications (2022)
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.
Keyphrases
  • gene expression
  • single molecule
  • high density
  • transcription factor
  • atomic force microscopy
  • dna methylation
  • genome wide
  • binding protein
  • high resolution
  • living cells
  • single cell
  • mass spectrometry