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
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.
