Tcf1 and Lef1 provide constant supervision to mature CD8⁺ T cell identity and function by organizing genomic architecture.

ABSTRACT: T cell identity is established during thymic development, but how it is maintained in the periphery remains unknown. Here we show that ablating Tcf1 and Lef1 transcription factors in mature CD8⁺ T cells aberrantly induces genes from non-T cell lineages. Using high-throughput chromosome-conformation-capture sequencing, we demonstrate that Tcf1/Lef1 are important for maintaining three-dimensional genome organization at multiple scales in CD8⁺ T cells. Comprehensive network analyses coupled with genome-wide profiling of chromatin accessibility and Tcf1 occupancy show the direct impact of Tcf1/Lef1 on the T cell genome is to promote formation of extensively interconnected hubs through enforcing chromatin interaction and accessibility. The integrative mechanisms utilized b

SUBMITTER: Shan Q 

PROVIDER: S-EPMC8494933 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature