Transcriptome analyses of tumor-adjacent somatic tissues reveal genes co-expressed with transposable elements
Transcriptome analyses of tumor-adjacent somatic tissues reveal genes co-expressed with transposable elements
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DOI：
10.1186/s13100-019-0180-5
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发表时间：
2019-09-03
期刊：
影响因子：
4.9
通讯作者：
Han, Mira V.
中科院分区：
文献类型：
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作者：
Chung, Nicky;Jonaid, G. M.;Han, Mira V.
尽管长期以来人们假设转座子通常只在生殖细胞中表达，但最近的证据表明转座因子（TE）序列的转录本经常在体细胞中发现。然而，TE转录水平在不同组织和不同个体之间的变化程度是未知的，并且TE和宿主基因mRNA之间的共表达尚未被检查。结果在这里，我们报告了TE衍生的转录水平的变化，在组织和个体之间观察到的非肿瘤组织收集的癌症基因组图谱。我们发现核心TE共表达模块主要由转座子组成，在广泛的TE类别中显示相关表达。尽管在组织内存在这种共表达，但当跨组织进行比较时，存在表现出组织特异性表达模式的个体TE基因座。核心TE模块与干扰素信号传导中免疫应答基因的其他基因模块呈负相关。KRAB锌指蛋白（KZFPs）是TE模块的过度表达基因成员，在多个组织中显示出正相关性。但是我们没有发现共表达的TE-KZFP对与已发表的ChIP-seq研究中结合的TE-KZFP对之间的重叠。结论：我们发现TE衍生的转录本在非肿瘤组织内和跨非肿瘤组织中存在意想不到的变异。我们描述了一个广泛的观点，RNA状态的非肿瘤组织表现出较高水平的TE转录。具有较高水平的TE转录物的组织具有广泛的TE共表达，具有大量KZFP的高表达，以及免疫基因的较低RNA水平。
Background Despite the long-held assumption that transposons are normally only expressed in the germ-line, recent evidence shows that transcripts of transposable element (TE) sequences are frequently found in the somatic cells. However, the extent of variation in TE transcript levels across different tissues and different individuals are unknown, and the co-expression between TEs and host gene mRNAs have not been examined. Results Here we report the variation in TE derived transcript levels across tissues and between individuals observed in the non-tumorous tissues collected for The Cancer Genome Atlas. We found core TE co-expression modules consisting mainly of transposons, showing correlated expression across broad classes of TEs. Despite this co-expression within tissues, there are individual TE loci that exhibit tissue-specific expression patterns, when compared across tissues. The core TE modules were negatively correlated with other gene modules that consisted of immune response genes in interferon signaling. KRAB Zinc Finger Proteins (KZFPs) were over-represented gene members of the TE modules, showing positive correlation across multiple tissues. But we did not find overlap between TE-KZFP pairs that are co-expressed and TE-KZFP pairs that are bound in published ChIP-seq studies. Conclusions We find unexpected variation in TE derived transcripts, within and across non-tumorous tissues. We describe a broad view of the RNA state for non-tumorous tissues exhibiting higher level of TE transcripts. Tissues with higher level of TE transcripts have a broad range of TEs co-expressed, with high expression of a large number of KZFPs, and lower RNA levels of immune genes.