TH cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes
TH cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes
复制标题
DOI：
10.1038/ni808
复制
发表时间：
2002-07-01
影响因子：
30.5
通讯作者：
Rao, A
中科院分区：
文献类型：
--
作者：
Avni, O;Lee, D;Rao, A
初始T细胞在用抗原刺激后分化成效应细胞，该过程伴随着效应细胞因子基因的染色质结构的变化。使用组蛋白乙酰化来评估这些变化，我们发现T细胞受体（TCR）刺激导致编码白细胞介素4和干扰素-γ的基因的早期激活。我们发现，在极化细胞因子的存在下，继续培养建立了两个细胞因子基因的组蛋白乙酰化的选择性模式，这与转录因子NFAT 1对这些基因调控区的限制性访问以及分化的T细胞的互斥基因表达相关。我们的数据指出了一个双相过程，其中细胞因子驱动的信号传导途径维持和加强由TCR引发的染色质结构变化。该过程确保细胞因子基因保持可接近相关转录因子，并促进诱导型转录因子NFAT与谱系特异性转录因子如加塔-3和T-bet的功能合作。
Naive T cells differentiate into effector cells upon stimulation with antigen, a process that is accompanied by changes in the chromatin structure of effector cytokine genes. Using histone acetylation to evaluate these changes, we showed that T cell receptor (TCR) stimulation results in early activation of the genes encoding both interleukin 4 and interferon-gamma. We found that continued culture in the presence of polarizing cytokines established a selective pattern of histone acetylation on both cytokine genes; this correlated with restricted access of the transcription factor NFAT1 to these gene regulatory regions as well as mutually exclusive gene expression by the differentiated T cells. Our data point to a biphasic process in which cytokine- driven signaling pathways maintain and reinforce chromatin structural changes initiated by the TCR. This process ensures that cytokine genes remain accessible to the relevant transcription factors and promotes functional cooperation of the inducible transcription factor NFAT with lineage-specific transcription factors such as GATA-3 and T-bet.