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首页> 外文期刊>Molecular and Cellular Biology >Regulation of the Il4 Gene Is Independently Controlled by Proximal and Distal 3′ Enhancers in Mast Cells and Basophils
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Regulation of the Il4 Gene Is Independently Controlled by Proximal and Distal 3′ Enhancers in Mast Cells and Basophils

机译：Il4基因的调控独立于肥大细胞和嗜碱性粒细胞的近端和远端3'增强子。

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Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3′ element contained conserved noncoding sequence 2 (CNS-2), which was a common enhancer for memory phenotype T cells, NKT cells, mast cells, and basophils. Targeted deletion of CNS-2 compromised production of IL-4 and several Th2 cytokines in connective-tissue-type and immature-type mast cells but not in basophils. Interestingly, the proximal 3′ element containing DNase I-hypersensitive site 4 (HS4), which controls Il4 gene silencing in T-lineage cells, exhibited selective enhancer activity in basophils. These results indicate that CNS-2 is an essential enhancer for Il4 gene transcription in mast cell but not in basophils. The transcription of the Il4 gene in mast cells and basophils is independently regulated by CNS-2 and HS4 elements that may be critical for lineage-specific Il4 gene regulation in these cell types.
机译：肥大细胞和嗜碱性粒细胞是建立对寄生虫感染的Th2保护反应的关键白介素4（IL-4）来源。肥大细胞 Il13 / Il4 位点的染色质结构和组蛋白修饰模式与产生IL-4的2型辅助T细胞相似。但是，使用转基因方法，我们发现在不同谱系的细胞类型中， Il4 基因表达受到各个 cis 调控元件的明显调控。远端3'元件包含保守的非编码序列2（CNS-2），其是记忆表型T细胞，NKT细胞，肥大细胞和嗜碱性粒细胞的常见增强子。 CNS-2的靶向缺失会损害结缔组织型和未成熟肥大细胞中IL-4和几种Th2细胞因子的产生，而嗜碱性粒细胞中则没有。有趣的是，在嗜碱粒细胞中，含有DNase I超敏位点4（HS4）的近端3'元件在T系细胞中控制 Il4 基因沉默，表现出选择性的增强子活性。这些结果表明CNS-2是肥大细胞中 Il4 基因转录的必需增强子，而不是嗜碱性粒细胞。肥大细胞和嗜碱性粒细胞中 Il4 基因的转录受CNS-2和HS4元件独立调节，这可能对这些细胞类型中的谱系特异性 Il4 基因调节至关重要。

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