Molaro Antoine, Malik Harmit S
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States; Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States.
Curr Opin Genet Dev. 2016 Apr;37:51-58. doi: 10.1016/j.gde.2015.12.001. Epub 2016 Jan 26.
Retroelements comprise a major fraction of most mammalian genomes. To protect their fitness and stability, hosts must keep retroelements in check in their germline. In most tissues mobile element insertions are decorated with chromatin modifications suggestive of transcriptional silencing. However, germline cells undergo massive chromatin reprogramming events, which erase repressive chromatin marks and necessitate de novo re-establishment of silencing. How do host genomes achieve the discrimination necessary for this de novo silencing? A series of recent studies have revealed aspects of the multi-pronged strategy that mammalian genomes use to identify and silence retroelements. These strategies include the use of small RNA-guides, of specialized DNA-binding protein adaptors and of proteins that repair chromatin discontinuities caused by retroelement insertions. Genetic analyses reveal the importance of these mechanisms of protection, each of which specializes in silencing retroelements of different evolutionary ages. Together, these strategies allow mammalian genomes to withstand the high burden of their parasites.
逆转录元件在大多数哺乳动物基因组中占很大一部分。为了保护自身的适应性和稳定性,宿主必须在其生殖系中控制逆转录元件。在大多数组织中,移动元件插入位点会被暗示转录沉默的染色质修饰所标记。然而,生殖系细胞会经历大规模的染色质重编程事件,这些事件会擦除抑制性染色质标记,并需要重新建立沉默机制。宿主基因组如何实现这种从头沉默所需的区分呢?最近的一系列研究揭示了哺乳动物基因组用于识别和沉默逆转录元件的多管齐下策略的各个方面。这些策略包括使用小RNA引导物、专门的DNA结合蛋白适配器以及修复由逆转录元件插入引起的染色质不连续性的蛋白质。遗传分析揭示了这些保护机制的重要性,每种机制都专门用于沉默不同进化年龄的逆转录元件。这些策略共同作用,使哺乳动物基因组能够承受其寄生元件的高负担。