biostudies-literatureUnknown211(13)Gao PIntramural NIH HHSE-proteins are TCR-sensitive transcription factors essential for intrathymic T cell transitions. Here, we show that deletion of E-proteins leads to both enhanced peripheral TGF-β-induced regulatory T (iT reg) cell and thymic naturally arising T reg cell (nT reg cell) differentiation. In contrast, deletion of Id proteins results in reduced nT reg cell differentiation. Mechanistic analysis indicated that decreased E-protein activity leads to de-repression of signaling pathways that are essential to Foxp3 expression. Decreased E-protein binding to an IL-2Rα enhancer locus facilitated TCR-induced IL-2Rα expression. Similarly, decreased E-protein activity facilitated TCR-induced NF-κB activation and generation of c-Rel. Consistent with this, microarray analysis indicated that cells with E-proteThe Journal of experimental medicine2651-68https://www.ebi.ac.uk/biostudies/studies/S-EPMC4267236biostudies-literatureDynamic changes in E-protein activity regulate T reg cell development.PMC4267236Zhang FYang ZGao PGardina PJStrober WFuss IJMyers TGHan XZhang QfalseDynamic changes in E-protein activity regulate T reg cell development.E-proteins are TCR-sensitive transcription factors essential for intrathymic T cell transitions. Here, we show that deletion of E-proteins leads to both enhanced peripheral TGF-β-induced regulatory T (iT reg) cell and thymic naturally arising T reg cell (nT reg cell) differentiation. In contrast, deletion of Id proteins results in reduced nT reg cell differentiation. Mechanistic analysis indicated that decreased E-protein activity leads to de-repression of signaling pathways that are essential to Foxp3 expression. Decreased E-protein binding to an IL-2Rα enhancer locus facilitated TCR-induced IL-2Rα expression. Similarly, decreased E-protein activity facilitated TCR-induced NF-κB activation and generation of c-Rel. Consistent with this, microarray analysis indicated that cells with E-prote2014-01-01T00:00:00Z2014 Dec2026-04-29T10:57:48.055Z2019-03-27T01:41:46ZS-EPMC42672362548898210.1084/jem.20132681