Key result
Perturbation of nuclear myosin VI disrupts RNA Polymerase II localization, alters chromatin organization, and decreases gene expression in mammalian cells.
Why the study?
The mechanisms concerning the assembly, organisation, and stability underpinning transcription factories in mammalian cells remained unknown.
Nuclear myosin VI acts as a molecular anchor that holds RNA Polymerase II into transcription factories, and its perturbation disrupts spatial regulation of gene expression.
MVI anchors RNAPII clusters to sustain transcription; leaves open whether selective inhibition could modulate gene expression in disease models.
SUMMARY 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 which underpin the function these transcription factories remain unknown. Here, we have used combination of single molecule imaging and genomic approaches to explore the role of nuclear myosin VI in the nanoscale organisation of RNAPII. We reveal that myosin VI acts as the molecular anchor that holds RNAPII into transcription factories. Perturbation of myosin VI leads to the disruption of RNAPII localisation, changes in chromatin organisation and subsequently a decrease in gene expression. Overall, we uncover the fundamental role of myosin VI in the spatial regulation of gene expression during the rapid response to changes in the cellular environment.
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Hari‐Gupta et al. (2020) studied this question. Perturbation of myosin VI was evaluated on RNAPII localization, chromatin organization, and gene expression. Perturbation of nuclear myosin VI disrupts RNA Polymerase II localization, alters chromatin organization, and decreases gene expression in mammalian cells.
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