What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation
What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation
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DOI：
10.1002/bies.201900232
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发表时间：
2020-02
期刊：
影响因子：
4
通讯作者：
M. Percharde;T. Sultana;M. Ramalho-Santos
中科院分区：
文献类型：
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作者：
M. Percharde;T. Sultana;M. Ramalho-Santos
转座因子（te）是当前或历史上可移动的序列，存在于所有真核生物基因组中。人们对te的调控和功能的兴趣日益浓厚，揭示了这些元素在进化、发育和疾病中的看似二分的作用。一方面，许多基因调控网络的组织归功于进化过程中通过TE动员的顺式元件和DNA结合位点的传播。另一方面，转座子不受控制的活性可以产生突变并导致包括癌症在内的疾病，而它们的表达增加也可能触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基本功能。本文主要讨论TEs的功能和调控，重点讨论哺乳动物中的LINE1。这表明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因子，如果在疾病环境中失去调控，这两种功能都可能是有害的。
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.