Back to Search
Start Over
DNA architectural protein CTCF facilitates subset-specific chromatin interactions to limit the formation of memory CD8+ T cells.
- Source :
-
Immunity (10747613) . May2023, Vol. 56 Issue 5, p959-959. 1p. - Publication Year :
- 2023
-
Abstract
- 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. [Display omitted] • Genome organization changes with effector CD8+ T cell differentiation • CTCF-binding patterns are altered with effector CD8+ T cell differentiation • CTCF regulates subset-specific transcriptional programs and chromatin accessibility • CTCF controls optimal CD8+ T cell-fate decisions in response to infection How changes in spatial chromatin organization are integrated into the network of molecular mechanisms mediating CD8+ T cell effector functions and memory formation is not well understood. Quon et al. characterize genome interactions accompanying the CD8+ T cell response to infection and find that the DNA architectural protein, CTCF, regulates the balance of terminally differentiated-effector cells and memory-fated cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10747613
- Volume :
- 56
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Immunity (10747613)
- Publication Type :
- Academic Journal
- Accession number :
- 163512842
- Full Text :
- https://doi.org/10.1016/j.immuni.2023.03.017