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Active maintenance of CD8+ T cell naivety through regulation of global genome architecture

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.

Cell reports (Cambridge), 2023-10, Vol.42 (10), p.113301-113301, Article 113301 [Periódico revisado por pares]

Elsevier Inc

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Título:
Active maintenance of CD8+ T cell naivety through regulation of global genome architecture
Autor: 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.
Assuntos: CD8+ T cell ; chromatin ; CP: Immunology ; CP: Molecular biology ; T cell memory
É parte de: Cell reports (Cambridge), 2023-10, Vol.42 (10), p.113301-113301, Article 113301
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
AUTHOR CONTRIBUTIONS
Conceptualization, B.E.R., S.Q., B.Y., and S.J.T.; methodology, B.E.R., J.L., K.T., and P.D.; investigation, B.E.R., B.Y., J.L., J.K.C., S.N., A.E.M., V.A.U., T.J.B., I.A.P., and A.L.S.; software, K.T.; formal analysis, B.E.R., K.T., P.D., M.O., Z.H., P.F.H., A.B., M.S., and D.P.; resources, A.K.; writing - original draft, B.E.R.; writing - reviewing & editing, B.E.R., S.J.T., S.Q., A.W.G., P.C., C.M., and A.K.; supervision, S.J.T., A.W.G., D.P., C.M., and P.C.; funding acquisition, S.J.T. A.W.G., and C.M.
Descrição: 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. [Display omitted] •CD8+ T cell differentiation states are underscored by distinct chromatin looping architectures•Chromatin loops connect CD8+ T cell subset-specific enhancers, transcription factors and genes•Effector and memory CTLs have similar genome architectures, explaining rapid memory recall•BACH2, and to a lesser extent, SATB1, enforce a naive CD8+ T cell loop architecture Russ et al. use Hi-C to map chromatin architecture dynamics during virus-specific CD8+ T cell differentiation. They demonstrate that key transcription factors preserve naivety by enforcing a naive chromatin state, and that effector and memory states are largely similar, providing a molecular explanation for rapid memory T cell function.
Editor: Elsevier Inc
Idioma: Inglês;Norueguês

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Active maintenance of CD8+ T cell naivety through regulation of global genome architecture

Elsevier Inc

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