Retrotransposons influence the mouse transcriptome: Implication for the divergence of genetic traits
Retrotransposons influence the mouse transcriptome: Implication for the divergence of genetic traits
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DOI：
10.1534/genetics.107.071647
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发表时间：
2007-06-01
期刊：
影响因子：
3.3
通讯作者：
Takeda, Junji
中科院分区：
文献类型：
--
作者：
Horie, Kyoji;Saito, Ei-suke;Takeda, Junji
逆转录转座子的大量积累占人类和小鼠基因组的40%，是基因组进化的主要事件之一。然而，大多数反转录转座子已经失去了反转录转座子的能力，这使得研究它们在基因组进化中的作用变得难以实现。胞内a粒子（IAP）元件是长末端重复（LTR）型小鼠反转录转座子，包括全长型和内部缺失型。一些具有逆转录转座子能力，并且在缺乏基因组防御系统的突变小鼠中报道了它们的活性上调，这表明IAP元件为研究逆转录转座子与哺乳动物基因组之间的相互作用提供了一个独特的平台。使用TAP元件作为模型案例，这里我们显示了反转录转座子的动员改变了小鼠的转录组。在培养细胞中进行的反转录转座试验表明，当提供功能性IAP蛋白时，内部缺失的TAP元件子集（称为I Delta 1型）可以有效地进行反转录转座。此外，I δ 1型IAP元件在侧翼区域表现出显著的转录诱导活性。胚胎干细胞全基因组转录分析鉴定了IAP诱导的转录物，包括IAP序列与内源基因之间的融合转录物。出乎意料的是，从129个小鼠品系的ES细胞中获得的这些TAP元件中有近一半在C57BL/6基因组中缺失，这表明iap驱动的转录有助于个体小鼠品系的独特性状。基于这些数据，我们提出逆转录转座子是形成哺乳动物转录组的驱动因素之一。
Massive accumulation of retrotransposons, comprising >40% of human and mouse genomes, is one of the major events in the evolution of the genome. However, most retrotransposons have lost retrotransposition competency, which makes studying their role in genome evolution elusive. Intracisternal A-particle (IAP) elements are long terminal repeat (LTR)-type mouse retrotransposons consisting of full-length and internally deleted types. Some are retrotransposition competent and their upregulated activity has been reported in Mutant mice deficient in genome defense systems, suggesting that IAP elements provide a unique platform for studying the interaction between retrotransposons and mammalian genomes. Using the TAP element as a model case, here we show that mobilization of retrotransposons alters the mouse transcriptome. Retrotransposition assay in cultured cells demonstrated that a subset of internally deleted TAP elements, called I Delta 1 type, retrotranspose efficiently when supplied with functional IAP proteins. Furthermore, the I Delta 1 type IAP element exhibited substantial transcription-inducing activity in the flanking region. Genomewide transcript analysis of embryonic stem (ES) cells identified IAP-induced transcripts, including fusion transcripts between IAP sequence and endogenous genes. Unexpectedly, nearly half of these TAP elements obtained from ES cells derived from 129 mouse strain were absent in the C57BL/6 genome, suggesting that IAP-driven transcription contributes to the unique trait of the individual mouse strain. On the basis of these data, we propose that retrotransposons are one of the drivers that shape the mammalian transcriptome.