title: c-Rel is required for chromatin remodeling across the IL-2 gene promoter.
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-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.
authors.affiliation: Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Sudha
authors.initials: S
authors.lastname: Rao
authors.forename: Steve
authors.initials: S
authors.lastname: Gerondakis
authors.forename: Donna
authors.initials: D
authors.lastname: Woltring
authors.forename: M Frances
authors.initials: MF
authors.lastname: Shannon
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000494:pharmacology; D017252:CD3 Complex / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000276:immunology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology; D020569:Proto-Oncogene Proteins c-rel / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D002843:Chromatin; D007376:Interleukin-2; D016328:NF-kappa B; D011506:Proteins; D020569:Proto-Oncogene Proteins c-rel; D051996:Transcription Factor RelA; C055927:endodeoxyribonuclease MseI; D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases