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. |