Molecular genetics of lung diseases group, Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München, GmbH, Ingolstadter, Landstrasse 1, D-85764, Neuherberg, Munich, Germany.
Respir Res. 2013 Oct 5;14(1):99. doi: 10.1186/1465-9921-14-99.
Transposable elements (TEs) are a class of mobile genetic elements (MGEs) that were long regarded as junk DNA, which make up approximately 45% of the genome. Although most of these elements are rendered inactive by mutations and other gene silencing mechanisms, TEs such as long interspersed nuclear elements (LINEs) are still active and translocate within the genome. During transposition, they may create lesions in the genome, thereby acting as epigenetic modifiers. Approximately 65 disease-causing LINE insertion events have been reported thus far; however, any possible role of TEs in complex disorders is not well established. Chronic obstructive pulmonary disease (COPD) is one such complex disease that is primarily caused by cigarette smoking. Although the exact molecular mechanism underlying COPD remains unclear, oxidative stress is thought to be the main factor in the pathogenesis of COPD. In this review, we explore the potential role of oxidative stress in epigenetic activation of TEs such as LINEs and the subsequent cascade of molecular damage. Recent advancements in sequencing and computation have eased the identification of mobile elements. Therefore, a comparative study on the activity of these elements and markers for genome instability would give more insight on the relationship between MGEs and complex disorder such as COPD.
转座元件（TEs）是一类移动遗传元件（MGEs），它们曾长期被视为“垃圾 DNA”，大约占基因组的 45%。尽管这些元件中的大多数因突变和其他基因沉默机制而失活，但长散布核元件（LINEs）等 TE 仍然活跃，并在基因组内转位。在转位过程中，它们可能会在基因组中造成损伤，从而充当表观遗传修饰物。迄今为止，已经报道了大约 65 种与疾病相关的 LINE 插入事件；然而，TE 在复杂疾病中的任何可能作用尚未得到很好的确立。慢性阻塞性肺疾病（COPD）就是这样一种复杂的疾病，主要由吸烟引起。尽管 COPD 的确切分子机制尚不清楚，但氧化应激被认为是 COPD 发病机制中的主要因素。在这篇综述中，我们探讨了氧化应激在 LINE 等 TE 的表观遗传激活以及随后的分子损伤级联反应中的潜在作用。测序和计算技术的最新进展使得识别移动元件变得更加容易。因此，对这些元件的活性和基因组不稳定性标志物进行比较研究，将有助于深入了解 MGEs 与 COPD 等复杂疾病之间的关系。
