Mechanisms of transcriptional regulation of the human IL-3/GM-CSF locus by inducible tissue-specific promoters and enhancers
Mechanisms of transcriptional regulation of the human IL-3/GM-CSF locus by inducible tissue-specific promoters and enhancers
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DOI：
10.1615/critrevimmunol.v24.i6.10
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发表时间：
2004-01-01
影响因子：
1.3
通讯作者：
Cockerill, PN
中科院分区：
文献类型：
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作者：
Cockerill, PN
IL-3 和 GM-CSF 基因在基因组中紧密相连，并且位于细胞因子基因簇内。 IL-3 和 GM-CSF 以高度诱导性和组织特异性模式表达，本综述试图提供该位点中控制其表达的关键调控元件的全面描述。尽管这些基因通常在 T 细胞中共表达，但它们在许多其他细胞类型中受到差异性调节，其中单核细胞和内皮细胞等细胞表达 GM-CSF，但不表达 IL-3。这表明它们可能受到不同机制的调节。该基因座中具有不同特异性的三个诱导增强子的鉴定强化了这一观点。这些增强子嵌入组织特异性 DNaseI 超敏感位点阵列中，这些位点很可能在建立不同的基因表达模式中发挥额外的作用。该位点还代表了一个有价值的模型系统，用于研究染色质重塑在细胞因子基因激活中的作用。 NFAT 是一种诱导因子，似乎在增强子内 DNaseI 超敏位点的形成中发挥重要作用，并且以与其他类别转录因子高度协作的方式发挥作用，以指导细胞因子基因表达的特定模式。
The IL-3 and GM-CSF genes are closely linked in the genome and reside within a cluster of cytokine genes. IL-3 and GM-CSF are expressed in a highly inducible and tissue-specific pattern, and this review attempts to provide a comprehensive description of the key regulatory elements in this locus that control their expression. Although these genes are typically coexpressed in T cells, they are differentially regulated in many other cell types, whereby cells such as monocytes and endothelial cells express GM-CSF, but not IL-3. This suggests that they are likely to be regulated by distinct mechanisms. This view is reinforced by the identification of three inducible enhancers in the locus that have different specificities. These enhancers are embedded within arrays of tissue-specific DNaseI hypersensitive sites that most likely play additional roles in establishing distinct patterns of gene expression. This locus also represents a valuable model system for studying the role of chromatin remodeling in cytokine gene activation. NFAT is one inducible factor that appears to play a major role in the formation of DNaseI hypersensitive sites within enhancers, and which functions in a highly cooperative manner with other classes of transcription factors to direct specific patterns of cytokine gene expression.