c-Rel Is Required for Chromatin Remodeling Across the IL-2 Gene Promoter
Date
2003
Authors
Rao, Sudha
Gerondakis, Steve
Woltring, Donna
Shannon, M Frances
Journal Title
Journal ISSN
Volume Title
Publisher
American Association of Immunologists
Abstract
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-κB 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.
Description
Keywords
Keywords: CD28 antigen; immunoglobulin enhancer binding protein; interleukin 2; restriction endonuclease; T lymphocyte receptor; transcription factor Rel; transcription factor RelA; unclassified drug; animal cell; article; binding site; chromatin; chromatin structu
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Source
Journal of Immunology
Type
Journal article