Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia.
Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia; Bioinformatics Platform, Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia.
Cell Rep. 2023 Oct 31;42(10):113301. doi: 10.1016/j.celrep.2023.113301. Epub 2023 Oct 19.
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.
幼稚 CD8 T 淋巴细胞分化为细胞毒性效应器和记忆 CTL 会导致转录和表型特征的大规模变化。目前对于基因组组织的大规模变化如何支持这些转录程序知之甚少。我们使用 Hi-C 来绘制幼稚、效应器和记忆病毒特异性 CD8 T 细胞中长程基因组接触的空间组织变化。我们观察到，幼稚 CD8 T 细胞的基因组结构与效应器和记忆基因组构型明显不同，与效应器/记忆分化相关的离散功能染色质域内有广泛的变化。幼稚 CD8 T 细胞中 BACH2 的缺失，或在较小程度上降低 SATB1 的 DNA 结合，会导致类似于效应器/记忆状态的染色质结构。这表明幼稚 CD8 T 细胞中的关键转录因子通过积极维持独特的幼稚染色质状态来抑制 T 细胞分化。
