摘要：SummaryWAPL, 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 thatin vivolymphopenic 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 followingin vitroandin vivostimulation, 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 cellsin vivoand demonstrate biological and clinical implications for its disruption by cohesin release factor WAPL.Graphical abstractDisplay OmittedHighlights•WAPL regulates chromatin loop extension in T cells•WAPL depletion disrupts cell cycling of T cells•WAPL deletion regulates allogeneic T cell responses and GVHDGenetics; Genomics; Molecular biology
