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

ABSTRACT: 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 c

SUBMITTER: Shan Q 

PROVIDER: S-EPMC9579964 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature