Migration through a small pore disrupts inactive chromatin organization in neutrophil-like cells

dc.contributor.authorJacobson, Elsie C.
dc.contributor.authorPerry, Jo K.
dc.contributor.authorLong, David S.
dc.contributor.authorOlins, Ada L.
dc.contributor.authorOlins, Donald E.
dc.contributor.authorWright, Bryon E.
dc.contributor.authorVickers, Mark H.
dc.contributor.authorO'Sullivan, Justin M.
dc.date.accessioned2018-12-17T20:49:39Z
dc.date.available2018-12-17T20:49:39Z
dc.date.issued2018-11-26
dc.description© The Author(s). 2018 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.description.abstractBackground. Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. The nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through confined spaces, where the nuclear shape must change in order to fit through a constriction. This occurs many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Here we characterized the effects of constricted migration in neutrophil-like cells.ResultsTotal RNA sequencing identified that migration of neutrophil-like cells through 5- or 14-m pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeletal remodeling.Hi-C was used to capture the genome organization in control and migrated cells. Limited switching was observed between the active (A) and inactive (B) compartments after migration. However, global depletion of short-range contacts was observed following migration with constriction compared to migration without constriction. Regions with disrupted contacts, TADs, and compartments were enriched for inactive chromatin.ConclusionShort-range genome organization is preferentially altered in inactive chromatin, possibly protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in relation tohuman health and disease.en_US
dc.description.sponsorshipHealth Research Council Explorer grant (HRC 15/604) to JMO. ECJ was a recipient of a University of Auckland doctoral scholarship, and Maurice Wilkins Centre travel grant.en_US
dc.identifier.citationElsie C. Jacobson, Jo K. Perry, David S. Long, Ada L. Olins, Donald E. Olins, Bryon E. Wright, Mark H. Vickers, Justin M. O’Sullivan. Migration through a small pore disrupts inactive chromatin organization in neutrophil-like cells. BMC Biology, 2018, Volume 16, Number 1, Page 1en_US
dc.identifier.issn1741-7007
dc.identifier.otherWOS:000451261700001
dc.identifier.urihttps://doi.org/10.1186/s12915-018-0608-2
dc.identifier.urihttp://hdl.handle.net/10057/15711
dc.language.isoen_USen_US
dc.publisherBioMed Central Ltd.en_US
dc.relation.ispartofseriesBMC Biology;v.16:no.1
dc.rights.holder© The Author(s). 2018en_US
dc.subjectMigrationen_US
dc.subjectHeterochromatinen_US
dc.subjectTranscriptionen_US
dc.subjectChromatin conformationen_US
dc.subjectEpigeneticsen_US
dc.subjectMechanotransductionen_US
dc.subjectNeutrophilen_US
dc.subjectImmuneen_US
dc.subjectHi-Cen_US
dc.subjectNuclear remodelingen_US
dc.titleMigration through a small pore disrupts inactive chromatin organization in neutrophil-like cellsen_US
dc.typeArticleen_US
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