Regulatory evolution of innate immunity through co-option of endogenous retroviruses.
Regulatory evolution of innate immunity through co-option of endogenous retroviruses.
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DOI：
10.1126/science.aad5497
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发表时间：
2016-03-04
期刊：
影响因子：
--
通讯作者：
Feschotte C
中科院分区：
文献类型：
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作者：
Chuong EB;Elde NC;Feschotte C
内源性逆转录病毒（ERVs）在哺乳动物基因组中大量存在，含有调节转录的序列。ERV的繁殖如何影响基因调控的进化仍然知之甚少。在这里，我们表明erv塑造了干扰素（IFN）反应的转录网络的进化，干扰素（IFN）反应是先天免疫的一个主要分支。我们发现，谱系特异性erv在不同的哺乳动物基因组中独立分散了许多ifn诱导增强子。CRISPR-Cas9缺失人类基因组中这些ERV元件的一个子集，会损害邻近ifn诱导基因的表达，并揭示它们参与基本免疫功能的调节，包括AIM2炎症小体的激活。虽然这些调控序列可能出现在古代病毒中，但它们现在构成了ifn诱导增强子的动态储存库，促进了哺乳动物免疫防御的遗传创新。
Endogenous retroviruses (ERVs) are abundant in mammalian genomes and contain sequences modulating transcription. How ERV propagation impacts the evolution of gene regulation remains poorly understood. Here we show that ERVs have shaped the evolution of a transcriptional network underlying the interferon (IFN) response, a major branch of innate immunity. We found that lineage-specific ERVs have dispersed numerous IFN-inducible enhancers independently in diverse mammalian genomes. CRISPR-Cas9 deletion of a subset of these ERV elements in the human genome impaired expression of adjacent IFN-induced genes and revealed their involvement in the regulation of essential immune functions, including activation of the AIM2 inflammasome. While these regulatory sequences likely arose in ancient viruses, they now constitute a dynamic reservoir of IFN-inducible enhancers fueling genetic innovation in mammalian immune defenses.