CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
Genome Res. 2019 Jan;29(1):40-52. doi: 10.1101/gr.235747.118. Epub 2018 Nov 19.
A few families of transposable elements (TEs) have been shown to evolve into -regulatory elements (CREs). Here, to extend these studies to all classes of TEs in the human genome, we identified widespread enhancer-like repeats (ELRs) and find that ELRs reliably mark cell identities, are enriched for lineage-specific master transcription factor binding sites, and are mostly primate-specific. In particular, elements of MIR and L2 TE families whose abundance co-evolved across chordate genomes, are found as ELRs in most human cell types examined. MIR and L2 elements frequently share long-range intra-chromosomal interactions and binding of physically interacting transcription factors. We validated that eight L2 and nine MIR elements function as enhancers in reporter assays, and among 20 MIR-L2 pairings, one MIR repressed and one boosted the enhancer activity of L2 elements. Our results reveal a previously unappreciated co-evolution and interaction between two TE families in shaping regulatory networks.
一些转座元件 (TEs) 家族已被证明能进化成调控元件 (CREs)。在这里，为了将这些研究扩展到人类基因组中的所有 TE 类别，我们鉴定出了广泛存在的增强子样重复 (ELRs)，并发现 ELRs 可靠地标示细胞身份，富含谱系特异性主转录因子结合位点，而且大多是灵长类特异性的。特别是，在脊索动物基因组中共同进化的 MIR 和 L2 TE 家族的元件，在大多数检查的人类细胞类型中都被鉴定为 ELRs。MIR 和 L2 元件经常共享长距离的染色体内相互作用和相互作用的转录因子的结合。我们验证了八个 L2 和九个 MIR 元件在报告基因检测中作为增强子发挥作用，在 20 个 MIR-L2 配对中，一个 MIR 抑制了 L2 元件的增强子活性，而一个增强了其活性。我们的研究结果揭示了两个 TE 家族在塑造调控网络方面的协同进化和相互作用，这是之前未被认识到的。
