Transcriptional landscape of repetitive elements in normal and cancer human cells

BMC Genomics

Nicola Neretti²  John M Sedivy¹  William Thompson²  Yue Zhang¹  Steven W Criscione¹ 

[1] Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA;Center for Computational Molecular Biology, Brown University, Providence, RI 02912, USA

关键词: ChIP-seq;    RNA-seq;    Repetitive element;    HERV;    LTR;    L1;    LINE-1;    Prostate cancer;    Transposable element;    Retrotransposon;   

Others  :  1216494
DOI  :  10.1186/1471-2164-15-583

 received in 2014-03-03, accepted in 2014-07-03,  发布年份 2014

【 摘 要 】

Background

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.

Results

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.

Conclusions

Our results support increased transcription of retrotransposons in transformed cells, which may explain the somatic retrotransposition events recently reported in several types of cancers.

【 授权许可】

   
2014 Criscione et al.; licensee BioMed Central Ltd.

【 图 表 】

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