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The comprehensive transcriptional analysis in Caenorhabditis elegans by integrating ChIP-seq and gene expression data

机译:通过整合ChIP-seq和基因表达数据对秀丽隐杆线虫进行全面的转录分析

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The fundamental step of learning transcriptional regulation mechanism is to identify the target genes regulated by transcription factors (TFs). Despite numerous target genes identified by chromatin immunoprecipitation followed by high-throughput sequencing technology (ChIP-seq) assays, it is not possible to infer function from binding alone in vivo. This is equally true in one of the best model systems, the nematode Caenorhabditis elegans (C. elegans), where regulation often occurs through diverse TF binding features of transcriptional networks identified in modENCODE. Here, we integrated ten ChIP-seq datasets with genome-wide expression data derived from tiling arrays, involved in six TFs (HLH-1, ELT-3, PQM-1, SKN-1, CEH-14 and LIN-11) with tissue-specific and four TFs (CEH-30, LIN-13, LIN-15B and MEP-1) with broad expression patterns. In common, TF bindings within 3 kb upstream of or within its target gene for these ten studies showed significantly elevated level of expression as opposed to that of non-target controls, indicated that these sites may be more likely to be functional through up-regulating its target genes. Intriguingly, expression of the target genes out of 5 kb upstream of their transcription start site also showed high levels, which was consistent with the results of following network component analysis. Our study has identified similar transcriptional regulation mechanisms of tissue-specific or broad expression TFs in C. elegans using ChIP-seq and gene expression data. It may also provide a novel insight into the mechanism of transcriptional regulation not only for simple organisms but also for more complex species.
机译:学习转录调控机制的基本步骤是识别受转录因子(TFs)调控的目标基因。尽管通过染色质免疫沉淀和高通量测序技术(ChIP-seq)分析鉴定出许多靶基因,但无法从体内单独结合推断功能。在最好的模型系统之一-线虫秀丽隐杆线虫中也是如此,其中调节通常通过modENCODE中识别的转录网络的多种TF结合特征来进行。在这里,我们将十个ChIP-seq数据集与来自切片阵列的全基因组表达数据进行了整合,涉及六个TF(HLH-1,ELT-3,PQM-1,SKN-1,CEH-14和LIN-11),组织特异性和四个具有广泛表达模式的TF(CEH-30,LIN-13,LIN-15B和MEP-1)。通常,针对这十项研究,在靶基因上游或靶基因内3 kb内的TF结合与非靶对照相比,表达水平显着升高,表明这些位点可能更可能通过上调来发挥功能其靶基因。有趣的是,靶基因在其转录起始位点上游5 kb的表达也显示出高水平,这与以下网络组成分析的结果一致。我们的研究已经使用ChIP-seq和基因表达数据确定了秀丽隐杆线虫组织特异性或广泛表达TFs的类似转录调控机制。它不仅可以为简单的生物而且为更复杂的物种提供转录调控机制的新颖见解。

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