Single molecule nanoscopy reveals that nuclear myosin VI regulates the spatial organization of mammalian transcription initiation

During transcription, RNA Polymerase II (RNAPII) is spatially organised into clusters that correlate with transcription activity. However, the assembly, organisation and stability of these transcription units remains unknown. Here, we have combined single molecule imaging with genomics approaches in order to explore the role of nuclear myosin VI in the nanoscale organisation of RNAPII. We can reveal that myosin VI acts as the molecular anchor that holds RNAPII into these transcription factories. Perturbation of myosin VI leads to the disruption of RNAPII localisation, changes in chromatin organisation and subsequently a decrease in gene expression. This role of Myosin VI is particularly important for transcription events following stimulation, where multiple genes are simultaneously activated. Overall design: Total RNA was extracted from three replicates of WT, MVI KD and Scrambled siRNA Hela cells.