GATA-3 directly remodels the IL-10 locus independently of IL-4 in CD4+ T cells
GATA-3 directly remodels the IL-10 locus independently of IL-4 in CD4+ T cells
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DOI：
10.4049/jimmunol.176.6.3470
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发表时间：
2006-03-15
影响因子：
4.4
通讯作者：
O'Garra, Anne
中科院分区：
文献类型：
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作者：
Shoemaker, John;Saraiva, Margarida;O'Garra, Anne
IL-10是炎症反应的主要调节因子。虽然各种转录因子被定义为增强IL-10，IL-10转录起始的分子机制仍然未知。6个不同的原代CD 4（+）T细胞群的mRNA谱显示转录因子加塔-3的差异表达与IL-10表达水平相关。我们发现加塔-3在初始的原代CD 4（+）T细胞中的异位表达增强了这些细胞的IL-10表达，并揭示了这种效应的可能机制。我们发现，加塔-3诱导的IL-10基因座的染色质结构的变化，这些变化甚至发生在IL-4的情况下。此外，我们发现在加塔-3的存在下，IL-10位点的组蛋白变得乙酰化。尽管在体内被募集到IL-10基因座上的两个位置，但加塔-3不反式激活IL-10启动子。因此，我们认为加塔-3在指导IL-10基因在原代CD 4（+）T细胞中表达中起着关键作用，可能是通过将IL-10基因座转换和稳定到转录活性状态。
IL-10 is a major regulator in inflammatory responses. Although various transcription factors were defined to enhance IL-10, the molecular mechanism for the initiation of Il-10 transcription, remains unknown. mRNA profiling of six distinct primary CD4(+) T cell populations showed differential expression of the transcription factor GATA-3 correlated with levels of IL-10 expression. We showed that ectopic expression of GATA-3 in naive primary CD4(+) T cells enhanced expression of IL-10 by these cells and uncovered a possible mechanism for this effect. We found that GATA-3 induced changes of the chromatin structure at the Il-10 locus and that these changes occur even in the absence of IL-4. Furthermore we found that in the presence of GATA-3 the histones at the Il-10 locus become acetylated. Despite being recruited in vivo to two locations on the Il-10 locus, GATA-3 did not transactivate the IL-10 promoter. We therefore suggest a key role of GATA-3 in instructing Il-10 gene expression in primary CD4(+) T cells, possibly by switching and stabilizing the Il-10 locus into a transcriptionally competent status.