Ye S K, Agata Y, Lee H C, Kurooka H, Kitamura T, Shimizu A, Honjo T, Ikuta K
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Immunity. 2001 Nov;15(5):813-23. doi: 10.1016/s1074-7613(01)00230-8.
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 Jgamma germline promoter and induces histone acetylation, germline transcription, and accessibility in Ba/F3 cells. We also show that histone acetylation of the TCRgamma 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 Jgamma germline promoter and control the accessibility of the TCRgamma locus by histone acetylation.
白细胞介素-7受体（IL-7R）在淋巴细胞发育过程中的扩增和V（D）J重组中发挥关键作用。在此，我们证明细胞因子刺激可迅速将Stat5和转录共激活因子募集至Jgamma种系启动子，并诱导Ba/F3细胞中的组蛋白乙酰化、种系转录和可及性。我们还表明，IL-7R缺陷型胸腺细胞中TCRgamma基因座的组蛋白乙酰化显著降低，而引入活性Stat5可恢复该基因座的组蛋白乙酰化和可及性。此外，用组蛋白脱乙酰酶抑制剂处理可恢复IL-7R缺陷型胸腺细胞中的组蛋白乙酰化和可及性。因此，这些结果表明，Stat5可能将转录共激活因子募集至Jgamma种系启动子，并通过组蛋白乙酰化控制TCRgamma基因座的可及性。
