Transcriptional landscape of repetitive elements in normal and cancer human cells.
Transcriptional landscape of repetitive elements in normal and cancer human cells.
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DOI：
10.1186/1471-2164-15-583
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发表时间：
2014-07-11
期刊：
影响因子：
4.4
通讯作者：
Neretti N
中科院分区：
文献类型：
--
作者：
Criscione SW;Zhang Y;Thompson W;Sedivy JM;Neretti N
重复元件至少占人类基因组的55%，最近估计高达三分之二。这些元件中的大多数是逆转录转座子，DNA序列可以通过“复制和粘贴”机制将自身拷贝插入新的基因组位置。这些移动的遗传元件在进化过程中对基因组的形成起着重要作用，并且与许多人类疾病的病因学有关。尽管它们的丰富性和多样性，很少有研究在全基因组范围内研究内源性反转录转座子的调控，主要是因为将高通量测序读数独特地映射到重复DNA的技术困难。在这里，我们开发了一种新的计算方法称为RepEnrich研究全基因组重复元件的转录调控。我们发现，人类中的许多长末端重复序列逆转录转座子在细胞系特异性方式中具有转录活性。与来自正常组织的细胞系相比，癌细胞系显示RNA聚合酶II与反转录转座子的结合增加。与癌细胞中反转录转座子的转录活性增加一致，我们发现前列腺肿瘤中L1反转录转座子RNA表达水平显著高于正常对照组。我们的研究结果支持逆转录转座子在转化细胞中的转录增加，这可以解释最近报道的几种类型的癌症中的体细胞逆转录转座事件。本文的补充材料可在10.1186/1471-2164-15-583获得，授权用户可以访问。
Repetitive elements comprise at least 55% of the human genome with more recent estimates as high as two-thirds. Most of these elements are retrotransposons, DNA sequences that can insert copies of themselves into new genomic locations by a “copy and paste” mechanism. These mobile genetic elements play important roles in shaping genomes during evolution, and have been implicated in the etiology of many human diseases. Despite their abundance and diversity, few studies investigated the regulation of endogenous retrotransposons at the genome-wide scale, primarily because of the technical difficulties of uniquely mapping high-throughput sequencing reads to repetitive DNA. Here we develop a new computational method called RepEnrich to study genome-wide transcriptional regulation of repetitive elements. We show that many of the Long Terminal Repeat retrotransposons in humans are transcriptionally active in a cell line-specific manner. Cancer cell lines display increased RNA Polymerase II binding to retrotransposons than cell lines derived from normal tissue. Consistent with increased transcriptional activity of retrotransposons in cancer cells we found significantly higher levels of L1 retrotransposon RNA expression in prostate tumors compared to normal-matched controls. Our results support increased transcription of retrotransposons in transformed cells, which may explain the somatic retrotransposition events recently reported in several types of cancers. Supplementary material is available for this article at 10.1186/1471-2164-15-583 and is accessible for authorized users.
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