التفاصيل البيبلوغرافية
| العنوان: |
Distinct use of super-enhancer elements controls cell type–specific CD25 transcription and function |
| المؤلفون: |
Spolski, Rosanne, Li, Peng, Chandra, Vivek, Shin, Boyoung, Goel, Shubham, Sakamoto, Keiko, Liu, Chengyu, Oh, Jangsuk, Ren, Min, Enomoto, Yutaka, West, Erin E., Christensen, Stephen M., Wan, Edwin C. K., Ge, Meili, Lin, Jian-Xin, Yan, Bingyu, Kazemian, Majid, Yu, Zu-Xi, Nagao, Keisuke, Vijayanand, Pandurangan, Rothenberg, Ellen V., Leonard, Warren J. |
| المصدر: |
Science Immunology, 8(89), eadi8217, (2023-11-03) |
| بيانات النشر: |
American Association for the Advancement of Science |
| سنة النشر: |
2023 |
| المجموعة: |
Caltech Authors (California Institute of Technology) |
| مصطلحات موضوعية: |
General Medicine, Immunology |
| الوصف: |
The IL-2 receptor α chain (IL-2Rα/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. ; © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. ; We thank N.Du for help with mast cell STAT5 ChIP-seq studies and K.Zhao for valuable discussions and critical comments. For ChIP-seq and RNA-seq analysis, DNA sequencing was performed in the NHLBI DNA Sequencing Core. ; Funding: This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI) (W.J.L.) and NIH grants R01AI135200 and R01HD100039 (E.V.R.) and R01AI121426 and R01HL114093 (P.V.). B.S. was supported by a Cancer Research Institute-Irvington Postdoctoral Fellowship. S.G., K.S., and K.N. were supported by the Intramural Research Program of NIAMS and the NIAMS Office of Scientific Technology ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
https://doi.org/10.1126/sciimmunol.adi8217 |
| DOI: |
10.1126/sciimmunol.adi8217 |
| الاتاحة: |
https://doi.org/10.1126/sciimmunol.adi8217 |
| Rights: |
info:eu-repo/semantics/openAccess ; No commercial reproduction, distribution, display or performance rights in this work are provided. |
| رقم الانضمام: |
edsbas.320C4FB2 |
| قاعدة البيانات: |
BASE |