Immunity 48, 243–257 (2018)

Lineage-determining transcription factors regulate chromatin accessibility and transcriptional output. In Immunity, Vahedi and colleagues show that the transcription factor TCF-1 controls T cell fate by targeting silent chromatin and inducing chromatin accessibility at T cell–specific loci. The authors observe three waves of chromatin remodeling during T cell development: at the ETP stage, the DN2b stage and the SP stage. TCF-1 shows the greatest enrichment for recognition sites and the most binding in regulatory regions that become accessible during the ETP and DN2b wave and persist until maturation, in both humans and mice. Chromatin accessibility is lost in these loci in TCF-1-deficient CD4+CD8+ double-positive thymocytes. Ectopic expression of TCF-1 induces de novo chromatin accessibility and expression of T cell–specific genes such as Bcl11b, Il2rb, Ccr7 and Icosl in non-hematopoietic cells such as fibroblasts.