Confined migration induces heterochromatin formation and alters chromatin accessibility

Chieh-Ren Hsia; Jawuanna McAllister; Ovais Hasan; Julius Judd; Seoyeon Lee; Richa Agrawal; Chao-Yuan Chang; Paul Soloway; Jan Lammerding

iScience (Sep 2022)

Confined migration induces heterochromatin formation and alters chromatin accessibility

Chieh-Ren Hsia,
Jawuanna McAllister,
Ovais Hasan,
Julius Judd,
Seoyeon Lee,
Richa Agrawal,
Chao-Yuan Chang,
Paul Soloway,
Jan Lammerding

Affiliations

Chieh-Ren Hsia: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Jawuanna McAllister: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA
Ovais Hasan: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA
Julius Judd: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
Seoyeon Lee: Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
Richa Agrawal: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA
Chao-Yuan Chang: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA
Paul Soloway: Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
Jan Lammerding: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA; Corresponding author

Journal volume & issue: Vol. 25, no. 9
p. 104978

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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