转座元件（TE）是重复的基因组元件，其中包含人类转录因子（TF）的结合位点。研究表明TE在胚胎发育和癌症等疾病的调控中起重要作用，但由于它们在基因组中广泛沉默，对它们功能的系统研究一直受到限制。在本文中，我们利用使用整个人类基因组文库的无偏大规模并行报告分析数据，鉴定具有功能增强子活性的TE在两种源于内胚层的人类癌症类型，结直肠癌和肝癌中的表达。我们展示了被鉴定的TE增强子具有与活性增强子相关的基因组特征，如表观遗传标记和TF结合。重要的是，我们发现TE的不同亚家族在组织特异性增强子中起作用，即在结直肠癌和肝癌中分别是MER11元件和LTR12元件。这些元件在每种细胞类型中都与不同的TF结合，并预测与差异表达基因有关联。总之，这些数据展示了不同癌症类型如何利用不同的TE作为组织特异性增强子，在全面理解TE作为癌基因中真正增强子的作用方面铺平了道路。© 2023. Springer Nature Limited.

Transposable elements (TE) are repetitive genomic elements that harbor binding sites for human transcription factors (TF). A regulatory role for TEs has been suggested in embryonal development and diseases such as cancer but systematic investigation of their functions has been limited by their widespread silencing in the genome. Here, we utilize unbiased massively parallel reporter assay data using a whole human genome library to identify TEs with functional enhancer activity in two human cancer types of endodermal lineage, colorectal and liver cancers. We show that the identified TE enhancers are characterized by genomic features associated with active enhancers, such as epigenetic marks and TF binding. Importantly, we identify distinct TE subfamilies that function as tissue-specific enhancers, namely MER11- and LTR12-elements in colon and liver cancers, respectively. These elements are bound by distinct TFs in each cell type, and they have predicted associations to differentially expressed genes. In conclusion, these data demonstrate how different cancer types can utilize distinct TEs as tissue-specific enhancers, paving the way for comprehensive understanding of the role of TEs as bona fide enhancers in the cancer genomes.© 2023. Springer Nature Limited.