Active maintenance of CD8+ T cell naivety through regulation of global genome architecture
- Author(s)
- Russ, BE; Barugahare, A; Dakle, P; Tsyganov, K; Quon, S; Yu, B; Li, J; Lee, JKC; Olshansky, M; He, Z; Harrison, PF; See, M; Nussing, S; Morey, AE; Udupa, VA; Bennett, TJ; Kallies, A; Murre, C; Collas, P; Powell, D; Goldrath, AW; Turner, SJ;
- Details
- Publication Year 2023-10-31,Volume 42,Issue #10,Page 113301
- Journal Title
- Cell Reports
- Publication Type
- Research article
- Abstract
- The differentiation of naive CD8(+) T lymphocytes into cytotoxic effector and memory CTL results in large-scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organization underpin these transcriptional programs. We use Hi-C to map changes in the spatial organization of long-range genome contacts within naive, effector, and memory virus-specific CD8(+) T cells. We observe that the architecture of the naive CD8(+) T cell genome is distinct from effector and memory genome configurations, with extensive changes within discrete functional chromatin domains associated with effector/memory differentiation. Deletion of BACH2, or to a lesser extent, reducing SATB1 DNA binding, within naive CD8(+) T cells results in a chromatin architecture more reminiscent of effector/memory states. This suggests that key transcription factors within naive CD8(+) T cells act to restrain T cell differentiation by actively enforcing a unique naive chromatin state.
- Publisher
- Cell Press
- Keywords
- *CD8-Positive T-Lymphocytes; *Chromatin; Cell Differentiation; Transcription Factors/genetics; Immunologic Memory/genetics; CD8+ T cell; CP: Immunology; CP: Molecular biology; T cell memory; chromatin
- Department(s)
- Laboratory Research
- PubMed ID
- 37858463
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2023.113301
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2023.113301- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-12-05 12:35:44
Last Modified: 2023-12-05 12:50:03