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Nuclear actin structure regulates chromatin accessibility.

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  • 1Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.

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Nuclear actin dynamics regulate chromatin accessibility and gene expression during mesenchymal stem cell differentiation. Inhibiting actin branching with CK666 alters chromatin structure and epigenetic marks, impacting cell fate.

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Area of Science:

  • Cell Biology
  • Epigenetics
  • Stem Cell Biology

Background:

  • Polymerized β-actin influences chromatin accessibility.
  • Nuclear actin transport guides mesenchymal stem cell (MSC) differentiation.
  • Actin dynamics play a role in nuclear organization and gene regulation.

Purpose of the Study:

  • To investigate the role of actin remodeling in regulating chromatin accessibility and MSC differentiation.
  • To determine how inhibiting specific actin-branching pathways affects nuclear actin structure and epigenetic modifications.
  • To explore the relationship between nuclear actin dynamics and gene expression patterns.

Main Methods:

  • Mesenchymal stem cells (MSCs) were treated with CK666 (Arp2/3 inhibitor) and cytochalasin D (CytoD).
  • Chromatin accessibility was assessed using ATAC-seq.
  • Nuclear actin structure and epigenetic marks (H3K9me3, H3K27me3) were visualized.
  • Arp4 knockdown was performed to study its role in transcription.

Main Results:

  • CK666 treatment decreased nuclear actin structure and altered chromatin accessibility (ATAC-seq), distinct from CytoD effects.
  • Arp2/3 inhibition reduced pericentric H3K9me3 marks, while CytoD redistributed H3K27me3 marks.
  • Arp4 knockdown caused chromatin unpacking but only a modest increase in transcription.
  • Observed chromatin landscape alterations correlated with differential gene expression and differentiation patterns.

Conclusions:

  • Dynamic actin remodeling is a key regulator of chromatin interactions and accessibility.
  • Specific actin-branching pathways differentially impact nuclear actin structure and epigenetic modifications.
  • Nuclear actin dynamics are crucial for guiding mesenchymal stem cell differentiation through chromatin regulation.