Ruminant-specific retrotransposons shape regulatory evolution of bovine immunity.
Ruminant-specific retrotransposons shape regulatory evolution of bovine immunity.
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DOI：
10.1101/gr.276241.121
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发表时间：
2022-08-25
期刊：
影响因子：
7
通讯作者：
Chuong, Edward B.
中科院分区：
文献类型：
--
作者：
Kelly, Conor J.;Chitko-McKown, Carol G.;Chuong, Edward B.
牛是一种重要的家畜物种，绘制农业相关性状（如疾病易感性）的基因组结构是牛研究界的一项重大挑战。谱系特异性转座因子（TE）越来越多地被认为有助于基因调控进化和变异，但这种可能性在反刍动物基因组中基本上未被探索。我们在牛细胞中进行了II型干扰素（IFN）反应的表观基因组分析，发现了数千个反刍动物特异性TE，包括MER41_BT和Bov-A2元件，预计可作为IFN诱导的增强子元件。牛细胞中的CRISPR敲除实验证实，包括IFNAR 2和IL 2 RB在内的关键免疫因子受TE衍生增强子的转录调控。最后，38个个体的群体基因组分析显示，多态性TE插入的子集可能在现代牛中起增强子的作用。我们的研究表明，谱系特异性TE塑造了反刍动物IFN反应的演变，并可能继续促进现代品种和个体之间的免疫基因调控差异。与以前在人类细胞中的工作一起，我们的研究结果表明，谱系特异性TE已被独立地增选来调节多个物种中的IFN诱导型基因表达，支持TE增选作为驱动IFN诱导型转录网络进化的经常性机制。
Cattle are an important livestock species, and mapping the genomic architecture of agriculturally relevant traits such as disease susceptibility is a major challenge in the bovine research community. Lineage-specific transposable elements (TEs) are increasingly recognized to contribute to gene regulatory evolution and variation, but this possibility has been largely unexplored in ruminant genomes. We conducted epigenomic profiling of the type II interferon (IFN) response in bovine cells and found thousands of ruminant-specific TEs including MER41_BT and Bov-A2 elements predicted to act as IFN-inducible enhancer elements. CRISPR knockout experiments in bovine cells established that critical immune factors including IFNAR2 and IL2RB are transcriptionally regulated by TE-derived enhancers. Finally, population genomic analysis of 38 individuals revealed that a subset of polymorphic TE insertions may function as enhancers in modern cattle. Our study reveals that lineage-specific TEs have shaped the evolution of ruminant IFN responses and potentially continue to contribute to immune gene regulatory differences across modern breeds and individuals. Together with previous work in human cells, our findings demonstrate that lineage-specific TEs have been independently co-opted to regulate IFN-inducible gene expression in multiple species, supporting TE co-option as a recurrent mechanism driving the evolution of IFN-inducible transcriptional networks.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
7
作者：
Gardner EJ;Lam VK;Harris DN;Chuang NT;Scott EC;Pittard WS;Mills RE;1000 Genomes Project Consortium;Devine SE
通讯作者：
Devine SE
影响因子：
4.9
作者：
Bao W;Kojima KK;Kohany O
通讯作者：
Kohany O
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Fulco, Charles P.;Nasser, Joseph;Engreitz, Jesse M.
通讯作者：
Engreitz, Jesse M.