Three-dimensional chromatin reorganization during CD8+ T cell activation is mediated by TRIM28

T cell activation is accompanied by extensive changes in epigenome. However, whether and how high-ordered chromatin organization is involved in CD8+ T cell activation is unclear. Here, we showed extensive changes in the three-dimensional genome during CD8+ T cell activation, associated with changes in gene transcription. Moreover, we identified Tripartite motif containing 28 (TRIM28) as an essential mediator in re-organization of spatial chromosomal interactions. Trim28 deficiency impaired CD8+ T cell activation in vitro and in vivo, due to its regulation on autocrine IL-2 production. Mechanistically, TRIM28 bound to genes associated with CD8+ T cell activation and promoted the formation of chromosomal loops. At the loop anchor regions, TRIM28 is likely recruited by CTCF, and required for binding of RNA Pol II and cohesin to form active chromosomal structure. These results thus identify a critical role of TRIM28-dependent chromatin topology in gene transcription during CD8+ T cell activation. Overall design: 1. To globally analyze the genes regulated by TRIM28, we performed RNA-seq analysis of Trim28fl/fl vs Trim28-/- CD8+ T cells activated in vitro. 2. To globally analyze the genes regulated by IL-2, we performed RNA-seq analysis of untreated vs anti-IL-2-treated CD8+ T cells in the presence of anti-CD3 and anti-CD28 for 3 days in vitro