First Author | Quon S | Year | 2023 |
Journal | Immunity | Volume | 56 |
Issue | 5 | Pages | 959-978.e10 |
PubMed ID | 37040762 | Mgi Jnum | J:335453 |
Mgi Id | MGI:7470620 | Doi | 10.1016/j.immuni.2023.03.017 |
Citation | Quon S, et al. (2023) DNA architectural protein CTCF facilitates subset-specific chromatin interactions to limit the formation of memory CD8(+) T cells. Immunity 56(5):959-978.e10 |
abstractText | Although the importance of genome organization for transcriptional regulation of cell-fate decisions and function is clear, the changes in chromatin architecture and how these impact effector and memory CD8(+) T cell differentiation remain unknown. Using Hi-C, we studied how genome configuration is integrated with CD8(+) T cell differentiation during infection and investigated the role of CTCF, a key chromatin remodeler, in modulating CD8(+) T cell fates through CTCF knockdown approaches and perturbation of specific CTCF-binding sites. We observed subset-specific changes in chromatin organization and CTCF binding and revealed that weak-affinity CTCF binding promotes terminal differentiation of CD8(+) T cells through the regulation of transcriptional programs. Further, patients with de novo CTCF mutations had reduced expression of the terminal-effector genes in peripheral blood lymphocytes. Therefore, in addition to establishing genome architecture, CTCF regulates effector CD8(+) T cell heterogeneity through altering interactions that regulate the transcription factor landscape and transcriptome. |