Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation
Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation
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DOI：
10.1016/s1074-7613(00)80642-1
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发表时间：
1998-12-01
期刊：
影响因子：
32.4
通讯作者：
Rao, A
中科院分区：
文献类型：
--
作者：
Agarwal, S;Rao, A
分化的细胞经历基因表达模式的程序性改变，这通常受染色质结构变化的调节。在这里，我们表明，T细胞分化的结果在长期的变化，在染色质结构的效应细胞因子基因，这坚持在休息的Th 1和Th 2细胞在没有进一步的刺激。幼稚T辅助细胞分化为成熟的Th 2细胞与IL-4和IL-13基因的染色质重塑相关，而分化为Th 1细胞引起IFN γ而不是IL-4或IL-13基因的重塑。IL-4基因座重塑伴随着去甲基化，需要抗原刺激和STAT 6激活。我们建议，染色质重塑的细胞因子基因位点的功能与生产性T细胞分化，并可能解释协调调节的Th 2细胞因子基因。
Differentiating cells undergo programmed alterations in their patterns of gene expression, which are often regulated by structural changes in chromatin. Here we demonstrate that T cell differentiation results in long-range changes in the chromatin structure of effector cytokine genes, which persist in resting Th1 and Th2 cells in the absence of further stimulation. Differentiation of naive T helper cells into mature Th2 cells is associated with chromatin remodeling of the IL-4 and IL-13 genes, whereas differentiation into Th1 cells evokes remodeling of the IFN gamma but not IL-4 or IL-13 genes. IL-4 locus remodeling is accompanied by demethylation and requires both antigen stimulation and STAT6 activation. We propose that chromatin remodeling of cytokine gene loci is functionally associated with productive T cell differentiation and may explain the coordinate regulation of Th2 cytokine genes.