MRC London Institute of Medical Sciences (LMS), London, W12 0NN, UK.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK.
Bioessays. 2020 Apr;42(4):e1900232. doi: 10.1002/bies.201900232. Epub 2020 Feb 13.
Transposable elements (TEs) are sequences currently or historically mobile, and are present across all eukaryotic genomes. A growing interest in understanding the regulation and function of TEs has revealed seemingly dichotomous roles for these elements in evolution, development, and disease. On the one hand, many gene regulatory networks owe their organization to the spread of cis-elements and DNA binding sites through TE mobilization during evolution. On the other hand, the uncontrolled activity of transposons can generate mutations and contribute to disease, including cancer, while their increased expression may also trigger immune pathways that result in inflammation or senescence. Interestingly, TEs have recently been found to have novel essential functions during mammalian development. Here, the function and regulation of TEs are discussed, with a focus on LINE1 in mammals. It is proposed that LINE1 is a beneficial endogenous dual regulator of gene expression and genomic diversity during mammalian development, and that both of these functions may be detrimental if deregulated in disease contexts.
转座元件 (TEs) 是目前或历史上可移动的序列，存在于所有真核生物基因组中。人们越来越感兴趣于理解 TEs 的调控和功能，揭示了这些元件在进化、发育和疾病中看似截然相反的作用。一方面，许多基因调控网络的组织得益于顺式元件的扩散和 DNA 结合位点通过 TE 在进化过程中的移动。另一方面，转座子的失控活动会产生突变并导致疾病，包括癌症，而它们的过度表达也可能引发导致炎症或衰老的免疫途径。有趣的是，最近发现 TEs 在哺乳动物发育过程中具有新的必需功能。在这里，讨论了 TEs 的功能和调控，重点是哺乳动物中的 LINE1。提出 LINE1 是哺乳动物发育过程中有益的内源性基因表达和基因组多样性的双重调节剂，如果在疾病环境中失调，这两种功能都可能有害。
