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首页> 外文期刊>Nature immunology >Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-gamma
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Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-gamma

机译:全面的表观遗传学分析可鉴定多个远端调控元件,指导编码干扰素-γ的基因转录

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摘要

Unlike the well defined T helper type 2 cytokine locus, little is known about the regulatory elements that govern the expression of Ifng, which encodes the 'signature' T helper type 1 cytokine interferon-gamma. Here our evolutionary analysis showed that the mouse Ifng locus diverged from the ancestral locus as a result of structural rearrangements producing deletion of the neighboring gene encoding interleukin 26 and disrupting synteny 57 kilobases upstream of Ifng. Proximal to that disruption, we identified by high-resolution mapping many regions with CD4(+) T cell subset-specific epigenetic modifications. A subset of those regions represented enhancers, whereas others blocked the activity of upstream enhancers or insulated Ifng from neighboring chromatin. Our findings suggest that proper expression of Ifng is maintained through the collective action of multiple distal regulatory elements present in a region of about 100 kilobases flanking Ifng.
机译:与定义良好的2型T辅助细胞因子基因座不同,关于控制Ifng表达的调控元件知之甚少,Ifng编码“签名”的1型T辅助细胞因子干扰素-γ。在这里,我们的进化分析显示,由于结构重排导致编码白介素26的邻近基因缺失并破坏了Ifng上游的57个碱基,小鼠Ifng基因座与祖先基因座发生了分化。接近该破坏,我们通过高分辨率映射许多区域来确定CD4(+)T细胞亚群特异性表观遗传修饰。这些区域的一部分代表增强子,而其他区域则阻止上游增强子的活性或使Ifng与邻近的染色质隔离。我们的发现表明,Ifng的正确表达通过在Ifng侧翼约100千碱基的区域中存在的多个远端调控元件的共同作用而得以维持。

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