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Publication : Active maintenance of CD8(+) T cell naivety through regulation of global genome architecture.

First Author  Russ BE Year  2023
Journal  Cell Rep Volume  42
Issue  10 Pages  113301
PubMed ID  37858463 Mgi Jnum  J:342875
Mgi Id  MGI:7548228 Doi  10.1016/j.celrep.2023.113301
Citation  Russ BE, et al. (2023) Active maintenance of CD8(+) T cell naivety through regulation of global genome architecture. Cell Rep 42(10):113301
abstractText  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.
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