Confined migration induces heterochromatin formation and alters chromatin accessibility

During migration, cells often squeeze through small constrictions, requiring extensive deformation. We hypothesized that nuclear deformation associated with such confined migration could alter chromatin organization and function. By studying cells migrating through microfluidic devices that mimic in...

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Bibliographic Details
Published in:iScience 2022-09, Vol.25 (9), p.104978-104978, Article 104978
Main Authors: Hsia, Chieh-Ren, McAllister, Jawuanna, Hasan, Ovais, Judd, Julius, Lee, Seoyeon, Agrawal, Richa, Chang, Chao-Yuan, Soloway, Paul, Lammerding, Jan
Format: Article
Language:English
Subjects:
Cell biology
Chromosome organization
Molecular biology
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Summary:During migration, cells often squeeze through small constrictions, requiring extensive deformation. We hypothesized that nuclear deformation associated with such confined migration could alter chromatin organization and function. By studying cells migrating through microfluidic devices that mimic interstitial spaces in vivo, we found that confined migration results in increased H3K9me3 and H3K27me3 heterochromatin marks that persist for days. This “confined migration-induced heterochromatin” (CMiH) was distinct from heterochromatin formation during migration initiation. Confined migration decreased chromatin accessibility at intergenic regions near centromeres and telomeres, suggesting heterochromatin spreading from existing sites. Consistent with the overall decrease in accessibility, global transcription was decreased during confined migration. Intriguingly, we also identified increased accessibility at promoter regions of genes linked to chromatin silencing, tumor invasion, and DNA damage response. Inhibiting CMiH reduced migration speed, suggesting that CMiH promotes confined migration. Together, our findings indicate that confined migration induces chromatin changes that regulate cell migration and other functions. [Display omitted] •Confined migration increases H3K9me3 and H3K27me3 heterochromatin marks•Confined migration-induced heterochromatin (CMiH) persists for days•Confined migration reduces chromatin accessibility near centromeres and telomeres•CMiH reduces transcription and facilitates efficient confined migration Cell biology; Chromosome organization; Molecular biology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2022.104978