Other
22 Authors
- Kazemian M,
- Shin B,
- Christensen SM,
- Li P,
- Leonard WJ,
- Nagao K,
- Liu C,
- Chandra V,
- Ge M,
- Wan ECK,
- Rothenberg EV,
- Yu ZX,
- Goel S,
- Vijayanand P,
- Spolski R,
- Oh J,
- Yan B,
- Enomoto Y,
- Sakamoto K,
- West EE,
- Ren M,
- Lin JX
| First Author | Spolski R | Year | 2023 |
| Journal | Sci Immunol | Volume | 8 |
| Issue | 89 | Pages | eadi8217 |
| PubMed ID | 37922339 | Mgi Jnum | J:364832 |
| Mgi Id | MGI:8172543 | Doi | 10.1126/sciimmunol.adi8217 |
| Citation | Spolski R, et al. (2023) Distinct use of super-enhancer elements controls cell type-specific CD25 transcription and function. Sci Immunol 8(89):eadi8217 |
| abstractText | The IL-2 receptor alpha chain (IL-2Ralpha/CD25) is constitutively expressed on double-negative (DN2/DN3 thymocytes and regulatory T cells (T(regs)) but induced by IL-2 on T and natural killer (NK) cells, with Il2ra expression regulated by a STAT5-dependent super-enhancer. We investigated CD25 regulation and function 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 T(regs), with these mice developing autoimmune alopecia, whereas deleting an intronic region decreased IL-2-induced CD25 on peripheral T and NK cells. Thus, distinct super-enhancer elements preferentially control constitutive versus inducible expression in a cell type-specific manner. The mediator-1 coactivator colocalized with specific STAT5-binding sites. Moreover, both upstream and intronic regions had extensive chromatin interactions, and deletion of either region altered the super-enhancer structure in mature T cells. These results demonstrate differential functions for distinct super-enhancer elements, thereby indicating previously unknown ways to manipulate CD25 expression in a cell type-specific fashion. |
