| Autor: |
Rao S; Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra, Australia., Gerondakis S, Woltring D, Shannon MF |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 Apr 01; Vol. 170 (7), pp. 3724-31. |
| DOI: |
10.4049/jimmunol.170.7.3724 |
| Abstrakt: |
IL-2 gene transcription occurs in an activation-dependent manner in T cells responding to TCR and CD28 activation. One of the critical events leading to increased IL-2 transcription is an alteration in chromatin structure across the 300-bp promoter region of the gene. We initially showed that IL-2 gene transcription in CD4(+) primary T cells is dependent on the NF-kappaB family member, c-Rel, but not RelA. We found that c-Rel is essential for global changes in chromatin structure across the 300-bp IL-2 promoter in response to CD3/CD28 in primary CD4(+) T cells, but not in response to pharmacological signals, paralleling the requirement for c-Rel in IL-2 mRNA and protein accumulation. Interestingly, measurement of activation-induced localized accessibility changes using restriction enzyme digestion revealed that accessibility close to the c-Rel binding site in the CD28RR region of the promoter is specifically dependent on c-Rel. In contrast, restriction enzyme sites located at a distance from the CD28RR behave independently of c-Rel. These results suggest a nonredundant role for c-Rel in generating a correctly remodeled chromatin state across the IL-2 promoter and imply that the strength of the signal determines the requirement for c-Rel. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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