The IL-7 receptor controls the accessibility of the TCRγ locus by Stat5 and histone acetylation

被引:152
作者
Ye, SK
Agata, Y
Lee, HC
Kurooka, H
Kitamura, T
Shimizu, A
Honjo, T
Ikuta, K [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Med Chem, Kyoto 6068501, Japan
[2] Kyoto Univ, Ctr Mol Biol & Genet, Kyoto 6068507, Japan
[3] Univ Tokyo, Inst Med Sci, Dept Hematopoiet Factors, Tokyo 1080071, Japan
关键词
D O I
10.1016/S1074-7613(01)00230-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The IL-7 receptor (IL-7R) plays critical roles in expansion and V(D)J recombination during lymphocyte development. Here we demonstrate that cytokine stimulation rapidly recruits Stat5 and transcriptional coactivators to the Jy germline promoter and induces histone acetylation, germline transcription, and accessibility in Ba/F3 cells. We also show that histone acetylation of the TCR gamma locus is significantly reduced in IL-7R-deficient thymocytes and that the introduction of active Stat5 restores the histone acetylation and accessibility of the locus. Furthermore, treatment with histone deacetylase inhibitor recovers the histone acetylation and accessibility in IL-7R-deficient thymocytes. Therefore, these results suggest that Stat5 may recruit the transcriptional coactivators to the Jy germline promoter and control the accessibility of the TCR gamma locus by histone acetylation.
引用
收藏
页码:813 / 823
页数:11
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