Russ Brendan E, Tsyganov Kirril, Quon Sara, Yu Bingfei, Li Jasmine, Lee Jason K C, Olshansky Moshe, He Zhaohren, Harrison Paul F, Barugahare Adele, 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
Department of Microbiology, Immunity Theme, Biomedical Discovery Institute, Monash University.
Bioinformatics platform, Biomedical Discovery Institute, Monash University, Australia.
bioRxiv. 2023 Feb 27:2023.02.26.530139. doi: 10.1101/2023.02.26.530139.
The differentiation of naïve CD8 cytotoxic T lymphocytes (CTLs) into effector and memory states results in large scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organisation reflect or underpin these transcriptional programs. We utilised Hi-C to map changes in the spatial organisation of long-range genome contacts within naïve, effector and memory virus-specific CD8 T cells. We observed that the architecture of the naive CD8 T cell genome was distinct from effector and memory genome configurations with extensive changes within discrete functional chromatin domains. However, deletion of the BACH2 or SATB1 transcription factors was sufficient to remodel the naïve chromatin architecture and engage transcriptional programs characteristic of differentiated cells. This suggests that the chromatin architecture within naïve CD8 T cells is preconfigured to undergo autonomous remodelling upon activation, with key transcription factors restraining differentiation by actively enforcing the unique naïve chromatin state.
初始CD8细胞毒性T淋巴细胞（CTL）分化为效应细胞和记忆细胞状态会导致转录和表型谱的大规模变化。关于基因组组织的大规模变化如何反映或支撑这些转录程序，我们知之甚少。我们利用Hi-C技术绘制了初始、效应和记忆病毒特异性CD8 T细胞内远程基因组接触的空间组织变化。我们观察到，初始CD8 T细胞基因组的结构与效应和记忆基因组构型不同，在离散的功能染色质结构域内有广泛变化。然而，删除BACH2或SATB1转录因子足以重塑初始染色质结构，并启动分化细胞特有的转录程序。这表明，初始CD8 T细胞内的染色质结构在激活时预先配置好进行自主重塑，关键转录因子通过积极维持独特的初始染色质状态来抑制分化。
