Cutting edge:: Histone acetylation and recombination at the TCRγ locus follows IL-7 induction

被引:42
作者
Huang, JQ
Durum, SK
Muegge, K
机构
[1] NCI, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA
[2] NCI, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA
关键词
D O I
10.4049/jimmunol.167.11.6073
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-7 signaling is required for V(D)J recombination at the TCR gamma locus. We have recently reported that IL-7 controls chromatin accessibility for RAG-mediated cleavage. Inhibition of histone deacetylase substituted for the IL-7 signal, indicating a role for histone acetylation in altering chromatin accessibility. We found a greatly reduced histone 3 and histone 4 acetylation level in IL-7R alpha (-/-) thymocytes in comparison with RAG(-/-) thymocytes or fetal thymocytes. Sterile transcripts, indicating an open chromatin configuration, were suppressed in IL-7R alpha (-/-) and IL-7(-/-)RAG(-/-) thymocytes. Moreover, exogenously added IL-7 induced sterile transcripts from the TCR gamma constant region in cultured thymocytes from IL-7(-/-)RAG(-/-) mice. This induction correlated with increased histone acetylation at the J-promoter and C-enhancer regulatory elements at the TCR gamma locus. These results suggest that IL-7 regulates chromatin accessibility for V(D)J recombination by specifically altering histone acetylation within the TCR gamma locus.
引用
收藏
页码:6073 / 6077
页数:5
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