BACKGROUND Transposable elements (TE) are commonly regarded as "junk DNA" with no apparent regulatory roles in the human genome. However, a growing body of evidence demonstrates that some TEs exhibit regulatory activities in a range of biological pathways and diseases, with notable examples in bile metabolism and innate immunity. TEs are typically suppressed by epigenetic modifications in healthy somatic tissues, which prevents both undesirable effects of insertional mutagenesis, and also unwanted gene activation. Interestingly, TEs are widely reported to be dysregulated in epithelial cancers, and while much attention has been paid to their effects on genome instability, relatively little has been reported on their effects on gene regulation. Here, we investigated the contribution of TEs to the transcriptional regulation in breast cancer cell lines. RESULTS We found that a subset of TE subfamilies were enriched in oncogenic transcription factor binding sites and also harboured histone marks associated with active transcription, raising the possibility of these subfamilies playing a broad role in breast cancer transcriptional regulation. To directly assess promoter activity in triple negative breast cancer cell lines, we identified four breast cancer-associated genes with putative TE-derived promoters. TE deletion confirmed a contribution to promoter activity in all cases, and for two examples the promoter activity was almost completely contained within the TE. CONCLUSIONS Our findings demonstrate that TEs provide abundant oncogenic transcription factor binding sites in breast cancer and that individual TEs contain substantial promoter activity. Our findings provide further evidence for transcriptional regulation of human genes through TE exaptation by demonstrating the regulatory potential of TEs in multiple breast cancer cell lines.

中文翻译：

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人类转座子是乳腺癌细胞系中转录因子结合位点和启动子活性的丰富来源。

背景技术转座因子(TE)通常被认为是“垃圾DNA”，在人类基因组中没有明显的调节作用。然而，越来越多的证据表明，一些 TE 在一系列生物途径和疾病中表现出调节活性，在胆汁代谢和先天免疫方面有显着的例子。TE 通常被健康体细胞组织中的表观遗传修饰所抑制，这既可以防止插入诱变的不良影响，也可以防止不需要的基因激活。有趣的是，广泛报道 TE 在上皮癌中失调，虽然人们对它们对基因组不稳定性的影响给予了很多关注，但关于它们对基因调控的影响的报道却相对较少。这里，我们研究了 TE 对乳腺癌细胞系转录调控的贡献。结果 我们发现一部分 TE 亚家族富含致癌转录因子结合位点，并且还含有与活跃转录相关的组蛋白标记，提高了这些亚家族在乳腺癌转录调控中发挥广泛作用的可能性。为了直接评估三阴性乳腺癌细胞系中的启动子活性，我们鉴定了四个乳腺癌相关基因与推定的 TE 衍生启动子。TE 缺失证实了在所有情况下对启动子活性的贡献，并且对于两个示例，启动子活性几乎完全包含在 TE 中。结论 我们的研究结果表明，TEs 在乳腺癌中提供了丰富的致癌转录因子结合位点，并且单个 TEs 含有大量的启动子活性。我们的研究结果通过证明 TE 在多种乳腺癌细胞系中的调节潜力，为通过 TE 扩展对人类基因的转录调控提供了进一步的证据。