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- W4309726419 abstract "Summary The IL-2 receptor α-chain (IL-2Rα/CD25) is constitutively expressed on DN2/DN3 thymocytes and Treg cells but induced by IL-2 on mature T and NK cells. Il2ra expression is regulated by a super-enhancer extensively bound by STAT5 in mature T cells. Here, we demonstrate that STAT5 cooperates with Notch to induce/maintain Il2ra/ CD25 expression in DN2/DN3 cells. Moreover, we systematically investigated CD25 regulation using a series of mice with deletions spanning STAT5 binding elements. Deleting the upstream super-enhancer region mainly affected constitutive CD25 expression on DN2/DN3 thymocytes and Tregs, whereas deleting an intronic region primarily decreased IL-2-induced CD25 on peripheral T and NK cells. Thus, distinct elements preferentially control constitutive versus inducible expression in a cell-type-specific manner, with the MED1 coactivator co-localizing with specific STAT5 binding sites. Moreover, the intronic region was a dominant element whose deletion altered the structure throughout the super-enhancer in mature T cells. These results demonstrate differential functions for distinct super-enhancer elements, thereby indicating ways to manipulate CD25 expression in a cell-type specific fashion." @default.
- W4309726419 created "2022-11-29" @default.
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- W4309726419 date "2022-11-18" @default.
- W4309726419 modified "2023-09-28" @default.
- W4309726419 title "Distinct super-enhancer elements differentially control<i>Il2ra</i>gene expression in a cell-type specific fashion" @default.
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- W4309726419 doi "https://doi.org/10.1101/2022.11.18.516445" @default.
- W4309726419 hasPublicationYear "2022" @default.
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