Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci
Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci
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DOI：
10.1074/jbc.m403688200
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发表时间：
2004-06-25
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：
Yamashita, M;Ukai-Tadenuma, M;Nakayama, T
GATA3表达对于2型辅助性T（Th2）细胞分化是必需的。GATA3介导的Th2细胞因子基因位点的染色质重塑，包括白细胞介素（IL）-13/IL-4基因位点的Th2特异性长范围组蛋白超乙酰化，发生在发育中的Th2细胞中。然而，很少有人知道GATA 3的作用，如果有的话，在维护已建立的重塑染色质在Th2细胞因子基因座。在这里，我们建立了一个Cre/LoxP为基础的位点特异性重组系统在培养的CD4 T细胞使用一个独特的腺病毒介导的基因转移技术。该系统使我们能够研究体外分化的Th2细胞中GATA 3表达丧失的影响。在GATA 3去除后，我们检测到所有Th2细胞因子的产生减少，IL-4基因位点的DNA甲基化增加，IL-5基因位点的组蛋白超乙酰化减少，但在IL-13/IL-4基因位点没有显着减少。因此，GATA 3在维持Th2表型和通过细胞分裂持续重塑特定Th2细胞因子基因座的染色质中起重要作用。
GATA3 expression is essential for type-2 helper T (Th2) cell differentiation. GATA3-mediated chromatin remodeling at the Th2 cytokine gene loci, including Th2-specific long range histone hyperacetylation of the interleukin (IL)-13/IL-4 gene loci, occurs in developing Th2 cells. However, little is known about the role of GATA3, if any, in the maintenance of established remodeled chromatin at the Th2 cytokine gene loci. Here, we established a Cre/LoxP-based site-specific recombination system in cultured CD4 T cells using a unique adenovirus-mediated gene transfer technique. This system allowed us to investigate the effect of loss of GATA3 expression in in vitro differentiated Th2 cells. After ablation of GATA3, we detected reduced production of all Th2 cytokines, increased DNA methylation at the IL- 4 gene locus, and decreased histone hyperacetylation at the IL- 5 gene locus but not significantly so at the IL-13/IL-4 gene loci. Thus, GATA3 plays important roles in the maintenance of the Th2 phenotype and continuous chromatin remodeling of the specific Th2 cytokine gene locus through cell division.