Nuclear actin structure regulates chromatin accessibility

• Published in: Nature communications 2024-05, Vol.15 (1), p.4095-15, Article 4095
• Main Authors: Sen, Buer, Xie, Zhihui, Thomas, Michelle D., Pattenden, Samantha G., Howard, Sean, McGrath, Cody, Styner, Maya, Uzer, Gunes, Furey, Terrence S., Rubin, Janet
• Format: Article
• Language: English
• Subjects: 13/100; 14/19; 49; 49/39; 631/337/100; 631/532/2074; 631/80/128; Accessibility; Actin; Actin-Related Protein 2-3 Complex - genetics; Actin-Related Protein 2-3 Complex - metabolism; Actins - metabolism; Animals; Cell Differentiation; Cell Nucleus - metabolism; Chromatin - metabolism; Chromatin Assembly and Disassembly; Chromatin remodeling; Cytochalasin D; Cytochalasin D - pharmacology; Differentiation; Gene expression; Histones - metabolism; Humanities and Social Sciences; Humans; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; multidisciplinary; Nuclear structure; Nuclei (cytology); Science; Science (multidisciplinary); Stem cells
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48580-y

Polymerized β-actin may provide a structural basis for chromatin accessibility and actin transport into the nucleus can guide mesenchymal stem cell (MSC) differentiation. Using MSC, we show that using CK666 to inhibit Arp2/3 directed secondary actin branching results in decreased nuclear actin structure, and significantly alters chromatin access measured with ATACseq at 24 h. The ATAC-seq results due to CK666 are distinct from those caused by cytochalasin D (CytoD), which enhances nuclear actin structure. In addition, nuclear visualization shows Arp2/3 inhibition decreases pericentric H3K9me3 marks. CytoD, alternatively, induces redistribution of H3K27me3 marks centrally. Such alterations in chromatin landscape are consistent with differential gene expression associated with distinctive differentiation patterns. Further, knockdown of the non-enzymatic monomeric actin binding protein, Arp4, leads to extensive chromatin unpacking, but only a modest increase in transcription, indicating an active role for actin-Arp4 in transcription. These data indicate that dynamic actin remodeling can regulate chromatin interactions. Intranuclear actin contributes to nuclear structure. Inducing actin remodeling within the nucleus regulates chromatin accessibility, and is associated with phenotypic outcomes in mesenchymal stem cells. As such, dynamic actin remodeling may modulate gene expression.