Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level
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DOI:
10.1016/j.bbrc.2013.07.074
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发表时间:
2013-08-23
影响因子:
3.1
通讯作者:
Madsen, Lone Bruhn
Madsen, Lone Bruhn
中科院分区:
生物学4区
文献类型:
--
作者:
Farajzadeh, Leila;Hornshoj, Henrik;Madsen, Lone Bruhn

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转录组是采样时组织或细胞中转录本的绝对集合。在本研究中,采用RNA-Seq对10种猪组织的转录组谱进行差异分析,以评估不同组织在基因和异构体表达水平上的差异,并分析转录起始位点、启动子使用和剪接的差异。总共测序了2.23亿个RNA片段,通过袖扣鉴定出59,930个转录基因位置和290,936个转录变体,与大约13,899个注释的人类基因相似。在基因水平上对组织进行差异表达的两两分析表明,来自猪脑的组织之间的差异最小。有趣的是,在组织对比中,异构体水平的相对差异表达水平通常没有变化。此外,对不同组织间启动子使用差异的分析显示,小脑(CBE)与额叶皮层、小脑与下丘脑(HYP)之间的差异比例高于其他比较。此外,差异转录起始位点的比较表明,与其他两两评估相比,包括下丘脑在内的比较中,这些位点的数量普遍增加。对其中一种组织对比的综合分析,即小脑与心脏在基因、异构体、转录起始位点(TSS)和启动子水平上的差异变异表明,有几个基因在所有四个水平上都存在差异。有趣的是,这些基因主要被注释到“电子传递链”和神经元分化,强调“组织重要”基因在多个水平上受到调控。此外,我们的分析表明,“跨组织方法”在筛选变异的可能解释时具有很好的潜力,例如在基因表达水平上观察到的变异。(C) 2013年作者。Elsevier Inc.出版。版权所有。
The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable the differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing.Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments.A comprehensive analysis of one of the tissue contrasts, i.e. cerebellum versus heart for differential variation at the gene, isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the "electron transport chain" and neuronal differentiation, emphasizing that "tissue important" genes are regulated at several levels. Furthermore, our analysis shows that the "across tissue approach" has a promising potential when screening for possible explanations for variations, such as those observed at the gene expression levels. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.