Hypomethylation of the proximal and intronic regulatory regions of the IFN-γ gene is not essential for its transcription by naive CD4+ T cells cultured with IL-4
Hypomethylation of the proximal and intronic regulatory regions of the IFN-γ gene is not essential for its transcription by naive CD4+ T cells cultured with IL-4
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DOI：
10.1016/s0165-2478(99)00078-4
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发表时间：
1999-08-03
影响因子：
4.4
通讯作者：
Furusho, K
中科院分区：
文献类型：
--
作者：
Kiyomasu, T;Katamura, K;Furusho, K
最近，有报道称，长期预先培养IL-4或IL-7可以诱导初始的CD4(+)T细胞产生干扰素-γ，而不需要通过TCR刺激。通过对干扰素-γ基因的TATA、近端和第一内含子调控区的研究，分析了IL-4预培养的初始CD4(+)T细胞中干扰素-γ转录的机制，并与典型的Th1细胞进行了比较。这些IL-4诱导的初始CD4(+)T细胞在PMA和离子霉素刺激下产生大量干扰素-γ，其两个调节区都完全甲基化，而Th1细胞中同样的低甲基化区域。DNase I超敏位点分析表明，IL-4诱导的初始CD4(+)T细胞的两个调控区对干扰素-γ的表达都不活跃。此外，我们还证明了在IL-4诱导的初始CD4(+)T细胞和Th1细胞中，能够与近端调控区结合的转录因子的组成是不同的。这些结果表明，参与CD4(+)T细胞表达干扰素-γ基因的转录机制因其在反应调节区和特定核因子中的分化方式而不同。(C)1999 Elsevier Science B.V.保留所有权利。
Recently, long-term preculture with IL-4 or IL-7 has been reported to induce IFN-gamma-producing ability in naive CD4(+) T cells without stimulation via TCR. The mechanism of IFN-gamma-transcription in naive CD4(+) T cells precultured with IL-4 was analyzed and compared with that in typical Th1 cells by focusing on the TATA proximal and first intronic regulatory regions of the IFN-gamma gene. Both regulatory regions in these IL-4-primed naive CD4(+) T cells, which produce a large amount of IFN-gamma upon stimulation with PMA and ionomycin, were completely methylated in contrast to the same hypomethylated regions in Th1 cells. DNase I hypersensitive site analysis suggested that both regulatory regions in IL-4-primed naive CD4(+) T cells were not active for IFN-gamma-expression. Moreover, we demonstrated that the composition of transcriptional factors that can bind to the proximal regulatory region is different between IL-4-primed naive CD4(+) T cells and Th1 cells. These results indicated that the transcriptional machinery involved in the expression of the IFN-gamma gene by CD4(+) T cells varied depending on their modes of differentiation in both the responsive regulatory regions and the specific nuclear factors. (C) 1999 Elsevier Science B.V. All rights reserved.