Rearrangement of T Cell genome architecture regulates GVHD

dc.contributor.authorSun, Yaping
dc.contributor.authorDotson, Gabrielle A.
dc.contributor.authorMuir, Lindsey A.
dc.contributor.authorRonquist, Scott
dc.contributor.authorOravecz-Wilson, Katherine
dc.contributor.authorPeltier, Daniel
dc.contributor.authorSeike, Keisuke
dc.contributor.authorLi, Lu
dc.contributor.authorMeixner, Walter
dc.contributor.authorRajapakse, Indika
dc.contributor.authorReddy, Pavan
dc.contributor.departmentPediatrics, School of Medicine
dc.date.accessioned2024-11-26T10:30:32Z
dc.date.available2024-11-26T10:30:32Z
dc.date.issued2022-08-06
dc.description.abstractWAPL, cohesin's DNA release factor, regulates three-dimensional (3D) chromatin architecture. The 3D chromatin structure and its relevance to mature T cell functions is not well understood. We show that in vivo lymphopenic expansion, and alloantigen-driven proliferation, alters the 3D structure and function of the genome in mature T cells. Conditional deletion of WAPL, cohesin's DNA release factor, in T cells reduced long-range genomic interactions and altered chromatin A/B compartments and interactions within topologically associating domains (TADs) of the chromatin in T cells at baseline. WAPL deficiency in T cells reduced loop extensions, changed expression of cell cycling genes and reduced proliferation following in vitro and in vivo stimulation, and reduced severity of graft-versus-host disease (GVHD) following experimental allogeneic hematopoietic stem cell transplantation. These data collectively characterize 3D genomic architecture of T cells in vivo and demonstrate biological and clinical implications for its disruption by cohesin release factor WAPL.
dc.eprint.versionFinal published version
dc.identifier.citationSun Y, Dotson GA, Muir LA, et al. Rearrangement of T Cell genome architecture regulates GVHD. iScience. 2022;25(9):104846. Published 2022 Aug 6. doi:10.1016/j.isci.2022.104846
dc.identifier.urihttps://hdl.handle.net/1805/44713
dc.language.isoen_US
dc.publisherElsevier
dc.relation.isversionof10.1016/j.isci.2022.104846
dc.relation.journaliScience
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourcePMC
dc.subjectGenetics
dc.subjectGenomics
dc.subjectMolecular biology
dc.titleRearrangement of T Cell genome architecture regulates GVHD
dc.typeArticle
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