What is it about?
Our lab published a series of papers that suggested that changes in nuclear actin structure could impact the phenotype of mesenchymal stem cells (MSC): increasing nuclear actin was associated with osteogenic differentiation while decreasing nuclear actin structure induced adipogenic differentiation. In this study, we show that compounds that increase and decrease actin polymerization within the nucleus robustly alter gene accessibility. Microscopy and novel molecular methods such as ATAC-seq were used to show that increasing – or decreasing - actin polymerization caused measurably different effects on gene accessibility, the location of histone mark and subsequently gene expression. We also considered whether increases in nuclear G-actin (actin monomers), which rise when the branching regulator Arp2/3 is inhibited involve other actin related proteins. As G-actin is bound by the intranuclear protein Arp4, we hypothesized that Arp4 localization might be key to specific gene access. Interestingly, knock down of Arp4 was associated with a scale order increase in globally accessible genes, but was not accompanied by comparable gene expression, indicating that Arp4 is necessary for transcription machinery to work.
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Why is it important?
A multitude of extracellular factors activate intracellular signals to modulate gene expression and stem cell differentiation. Nuclear genetic material (chromatin) upon which these signals act is positioned on a presumably stable nucleoskeleton consisting of intermediate filament lamin proteins. However, within the nucleus, an entire toolbox for remodeling actin structure exists, alongside a regulated system to traffic actin into and out of the nucleus. We have shown that rearrangements of intranuclear actin structure reposition chromatin with resultant changes in gene accessibility.
Perspectives
[Perspective provided by author Dr. Janet Rubin] : Not only does this confirm that actin is a structural component of the nucleoskeleton, but actin itself offers a new structural target within the nucleus – one that is susceptible to real time modification – upon which a cell’s epigenetic potential is written.
Dr Maya Styner
University of North Carolina at Chapel Hill, Department of Medicine, Division of Endocrinology
Read the Original
This page is a summary of: Nuclear actin structure regulates chromatin accessibility, Nature Communications, May 2024, Springer Science + Business Media,
DOI: 10.1038/s41467-024-48580-y.
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