Biology Department, Johns Hopkins University, Baltimore, MD 21218, USA.
Mutat Res. 2011 Sep 1;714(1-2):95-104. doi: 10.1016/j.mrfmmm.2011.05.002. Epub 2011 May 11.
Integrity of the germline genome is essential for the production of viable gametes and successful reproduction. In mammals, the generation of gametes involves extensive epigenetic changes (DNA methylation and histone modification) in conjunction with changes in chromosome structure to ensure flawless progression through meiotic recombination and packaging of the genome into mature gametes. Although epigenetic reprogramming is essential for mammalian reproduction, reprogramming also provides a permissive window for exploitation by transposable elements (TEs), autonomously replicating endogenous elements. Expression and propagation of TEs during the reprogramming period can result in insertional mutagenesis that compromises genome integrity leading to reproductive problems and sporadic inherited diseases in offspring. Recent work has identified the germ cell associated PIWI Interacting RNA (piRNA) pathway in conjunction with the DNA methylation and histone modification machinery in silencing TEs. In this review we will highlight these recent advances in piRNA mediated regulation of TEs in the mouse germline, as well as mention the repercussions of failure to properly regulate TEs.
生殖细胞基因组的完整性对于产生有活力的配子和成功繁殖至关重要。在哺乳动物中，配子的产生涉及广泛的表观遗传变化（DNA 甲基化和组蛋白修饰）以及染色体结构的变化，以确保减数分裂重组的完美进行，并将基因组包装成成熟的配子。尽管表观遗传重编程对于哺乳动物的繁殖是必不可少的，但重编程也为转座元件（TEs）的利用提供了一个许可窗口，TEs 是自主复制的内源性元件。在重编程期间，TEs 的表达和传播可能导致插入突变，从而损害基因组的完整性，导致后代出现生殖问题和散发性遗传疾病。最近的研究工作已经确定了与 DNA 甲基化和组蛋白修饰机制一起在沉默 TEs 中发挥作用的生殖细胞相关 PIWI 相互作用 RNA (piRNA) 途径。在这篇综述中，我们将重点介绍小鼠生殖细胞中 piRNA 介导的 TEs 调节的这些最新进展，并提到未能正确调节 TEs 的后果。
