CD28 costimulation controls histone hyperacetylation of the interleukin 5 gene locus in developing Th2 cells
CD28 costimulation controls histone hyperacetylation of the interleukin 5 gene locus in developing Th2 cells
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DOI：
10.1074/jbc.m401248200
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发表时间：
2004-05-28
影响因子：
4.8
通讯作者：
Nakayama, T
中科院分区：
文献类型：
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作者：
Inami, M;Yamashita, M;Nakayama, T
白细胞介素5（IL - 5）在过敏性炎症反应中具有独特作用，了解产生IL - 5的细胞生成的分子机制对于调控过敏性疾病至关重要。初始CD4 T细胞分化为2型辅助性T（Th2）细胞伴随着染色质重塑，包括与IL - 4、IL - 13和IL - 5基因相关的核小体中组蛋白H3和H4的高度乙酰化。与IL - 4和IL - 13基因相比，IL - 5基因的组蛋白高度乙酰化呈现出延迟的动力学特征，这表明IL - 5基因位点具有独特的重塑机制。在此我们研究了CD28共刺激在产生IL - 5的细胞生成以及IL - 5基因位点组蛋白高度乙酰化中的作用。CD28共刺激选择性地增强了IL - 5基因位点的组蛋白高度乙酰化，这似乎是通过NF - κB激活以及随后GATA3的上调所介导的。CD28共刺激敏感的组蛋白高度乙酰化几乎跨越了IL - 5和RAD50之间的整个基因间区域，并伴有基因间转录本。因此，这首次证明了CD28共刺激在Th2细胞分化过程中控制染色质重塑过程。
Interleukin 5 ( IL-5) plays a unique role in allergic inflammatory responses, and the understanding of molecular mechanisms underlying the generation of IL-5-producing cells is crucial for the regulation of allergic disorders. Differentiation of naive CD4 T cells into type-2 helper (Th2) cells is accompanied by chromatin remodeling including hyperacetylation of histones H3 and H4 in the nucleosomes associated with the IL-4, IL-13, and IL-5 genes. Histone hyperacetylation of the IL-5 gene displayed a delayed kinetics compared with that of the IL-4 and IL-13 genes, suggesting a distinct remodeling mechanism for the IL-5-gene locus. Here we studied the role of CD28 costimulation in the generation of IL-5-producing cells and the histone hyperacetylation of the IL-5 gene locus. CD28-costimulation selectively enhanced histone hyperacetylation of the IL-5 gene locus that appeared to be mediated through NF-kappaB activation and subsequent up-regulation of GATA3. The CD28 costimulation-sensitive histone hyperacetylation spanned almost the entire intergenic region between the IL-5 and RAD50 accompanied with intergenic transcript. Thus, this is the first demonstration that CD28 costimulation controls a chromatin-remodeling process during Th2 cell differentiation.