Tcf1-CTCF cooperativity shapes genomic architecture to promote CD8+ T cell homeostasis.

Qiang Shan, Shaoqi Zhu, Xia Chen, Jia Liu, Shuang Yuan, Xiang Li, Weiqun Peng, Hai-Hui Xue

Nature immunology 2022 Aug

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CD8+ T cell homeostasis is maintained by the cytokines IL-7 and IL-15. Here we show that transcription factors Tcf1 and Lef1 were intrinsically required for homeostatic proliferation of CD8+ T cells. Multiomics analyses showed that Tcf1 recruited the genome organizer CTCF and that homeostatic cytokines induced Tcf1-dependent CTCF redistribution in the CD8+ T cell genome. Hi-C coupled with network analyses indicated that Tcf1 and CTCF acted cooperatively to promote chromatin interactions and form highly connected, dynamic interaction hubs in CD8+ T cells before and after cytokine stimulation. Ablating CTCF phenocopied the proliferative defects caused by Tcf1 and Lef1 deficiency. Tcf1 and CTCF controlled a similar set of genes that regulated cell cycle progression and promoted CD8+ T cell homeostatic proliferation in vivo. These findings identified CTCF as a Tcf1 cofactor and uncovered an intricate interplay between Tcf1 and CTCF that modulates the genomic architecture of CD8+ T cells to preserve homeostasis. © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Citation

Qiang Shan, Shaoqi Zhu, Xia Chen, Jia Liu, Shuang Yuan, Xiang Li, Weiqun Peng, Hai-Hui Xue. Tcf1-CTCF cooperativity shapes genomic architecture to promote CD8+ T cell homeostasis. Nature immunology. 2022 Aug;23(8):1222-1235