| First Author | Sun Y | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 9 | Pages | 104846 |
| PubMed ID | 36043052 | Mgi Jnum | J:327997 |
| Mgi Id | MGI:7334460 | Doi | 10.1016/j.isci.2022.104846 |
| Citation | Sun Y, et al. (2022) Rearrangement of T Cell genome architecture regulates GVHD. iScience 25(9):104846 |
| abstractText | WAPL, 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. |
