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Tissue-Specific Chromatin Modifications at a Multigene Locus Generate Asymmetric Transcriptional Interactions

机译:在多基因位点的组织特定染色质修饰产生不对称的转录相互作用。

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摘要

Random assortment within mammalian genomes juxtaposes genes with distinct expression profiles. This organization, along with the prevalence of long-range regulatory controls, generates a potential for aberrant transcriptional interactions. The human CD79b/GH locus contains six tightly linked genes with three mutually exclusive tissue specificities and interdigitated control elements. One consequence of this compact organization is that the pituitarycell-specific transcriptional events that activate hGH-N also trigger ectopic activation of CD79b. However, the B-cell-specific events that activate CD79b do not trigger reciprocal activation of hGH-N. Here we utilized DNase I hypersensitive site mapping, chromatin immunoprecipitation, and transgenic models to explore the basis for this asymmetric relationship. The results reveal tissue-specific patterns of chromatin structures and transcriptional controls at the CD79b/GH locus in B cells distinct from those in the pituitary gland and placenta. These three unique transcriptional environments suggest a set of corresponding gene expression pathways and transcriptional interactions that are likely to be found juxtaposed at multiple sites within the eukaryotic genome.
机译:哺乳动物基因组内的随机分类使具有不同表达特征的基因并列。该组织以及广泛的远程调节控制,产生了异常转录相互作用的潜力。人CD79b / GH基因座包含六个紧密相连的基因,具有三个互斥的组织特异性和相互交叉的控制元件。这种紧密组织的结果是激活hGH-N的垂体细胞特异性转录事件也触发CD79b的异位激活。但是,激活CD79b的B细胞特定事件不会触发hGH-N的相互激活。在这里,我们利用DNase I超敏位点作图,染色质免疫沉淀和转基因模型来探索这种不对称关系的基础。结果揭示了不同于垂体和胎盘的B细胞CD79b / GH位点的染色质结构和转录控制的组织特异性模式。这三个独特的转录环境提示可能在真核基因组内多个位置并列的一组相应的基因表达途径和转录相互作用。

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