https://orcid.org/0000-0001-6190-196X
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ABSTRACT
Cell migration involves the actin cytoskeleton, and recently recognized nuclear involvement. In this study, we explore the impact of chromatin remodeling on cell migration using NIH 3T3 cells and a scratch wound assay subjected to pharmacological interventions. We inhibit histone deacetylases (HDACs) with Trichostatin A (TSA) and methyltransferase EZH2 with GSK126 to modulate chromatin compaction. Our results indicate that chromatin modifications impair wound closure efficiency, reduce individual cell migration speed, and disrupt migration persistence. Live-cell imaging reveals dynamic intranuclear chromatin remodeling and nuclear shape parameters during migration, influenced by both small- and large-scale chromatin remodeling. The altered nuclear shape is associated with disrupted cell and nuclear mechanics, suggesting a crucial interplay between chromatin remodeling, nuclear mechanics and migration. These findings shed light on the intricate connection between intranuclear chromatin dynamics, nuclear mechanics, and cell migration, providing a basis for further investigations into the molecular mechanisms governing these processes.
Acknowledgments
The authors are grateful to the Corey Neu’s lab at University of Colorado Boulder for the NIH 3T3 cells.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
S.G. conceived of the project. J.F., B.H., and S.G. conducted experiments. J.F., B.H., S.K. and S.G. contributed to data analysis. S.G. wrote the manuscript with input from all authors. S.G. secured resources and funding for this study.
Data availability statement
The authors confirm that the data supporting the findings of this study are available in the article and its supplementary materials.