@article{a0686ac32aee48ab8bf176a06761e65f,
title = "Active maintenance of CD8+ T cell naivety through regulation of global genome architecture",
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.",
keywords = "CD8+ T cell, chromatin, CP: Immunology, CP: Molecular biology, T cell memory",
author = "Russ, {Brendan E.} and Adele Barugahare and Pushkar Dakle and Kirril Tsyganov and Sara Quon and Bingfei Yu and Jasmine Li and Lee, {Jason K.C.} and Moshe Olshansky and Zhaohren He and Harrison, {Paul F.} and Michael See and Simone Nussing and Morey, {Alison E.} and Udupa, {Vibha A.} and Bennett, {Taylah J.} and Axel Kallies and Cornelis Murre and Phillipe Collas and David Powell and Goldrath, {Ananda W.} and Turner, {Stephen J.}",
note = "Funding Information: We thank the Monash Flowcore facility (Monash University, Clayton) for helpful advice and technical assistance with flow cytometry and cell-sorting experiments and the Monash Micromon Genomics (Monash University, Clayton) and Hudson Genomics (Hudson Institute, Monash University Health and Medical Precinct, Clayton) facilities for advice relating to preparation and sequencing of Hi-C and ATAC-seq samples. Bioinformatic analyses were performed by the Monash Bioinformatics Platform, and mice were bred and housed at the Monash Animal Research Platform at Monash University, Clayton. Thanks to the Goldrath, Turner, and La Gruta laboratories for technical advice, helpful discussion, and critical reading of the manuscript. This work was supported by grants from the National Health and Medical Research Council of Australia, APP1003131 (S.J.T.); an Australian Research Council Discovery Grant, DP170102020 (S.J.T.); a joint Monash University-University of California, San Diego Seed Development grant (S.J.T. and A.W.G.); an NIH P01AI13212 (A.W.G.) and NIH grant AI102853 (C.M.). 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. A.W.G. is a member of the scientific advisory board of ArsenalBio. No funding from ArsenalBio was provided for this work. We support inclusive, diverse, and equitable conduct of research. Funding Information: We thank the Monash Flowcore facility (Monash University, Clayton) for helpful advice and technical assistance with flow cytometry and cell-sorting experiments and the Monash Micromon Genomics (Monash University, Clayton) and Hudson Genomics (Hudson Institute, Monash University Health and Medical Precinct, Clayton) facilities for advice relating to preparation and sequencing of Hi-C and ATAC-seq samples. Bioinformatic analyses were performed by the Monash Bioinformatics Platform, and mice were bred and housed at the Monash Animal Research Platform at Monash University, Clayton. Thanks to the Goldrath, Turner, and La Gruta laboratories for technical advice, helpful discussion, and critical reading of the manuscript. This work was supported by grants from the National Health and Medical Research Council of Australia, APP1003131 (S.J.T.); an Australian Research Council Discovery Grant, DP170102020 (S.J.T.); a joint Monash University - University of California, San Diego Seed Development grant (S.J.T. and A.W.G.); an NIH P01AI13212 (A.W.G.) and NIH grant AI102853 (C.M.). Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = oct,
day = "31",
doi = "10.1016/j.celrep.2023.113301",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "10",
}