Active maintenance of CD8+ T cell naivety through regulation of global genome architecture
Authors:
- Russ, Brendan E.
- Barugahare, Adele
- Dakle, Pushkar
- Tsyganov, Kirril
- Quon, Sara
- Yu, Bingfei
- Li, Jasmine
- Lee, Jason K.C.
- Olshansky, Moshe
- He, Zhaohren
- Harrison, Paul F.
- See, Michael
- Nussing, Simone
- Morey, Alison E.
- Udupa, Vibha A.
- Bennett, Taylah J.
- Kallies, Axel
- Murre, Cornelis
- Collas, Phillipe
- Powell, David
- Goldrath, Ananda W.
- Turner, Stephen J.
Details:
Cell Reports, Volume 42, Issue 10, 2023-10-31
Article Link: Click here
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.