Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages
Alveolar macrophages (AMs) form the first defense line against various respiratory pathogens, and their immune response has a profound impact on the outcome of respiratory infection. Enhancer of zeste homolog 2 (EZH2), which catalyzes the trimethylation of H3K27 for epigenetic repression, has gained...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2394 |
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| author | Liangliang Zhang Jian Jin Weiyun Qin Jing Jiang Wenbin Bao Ming-an Sun |
| author_facet | Liangliang Zhang Jian Jin Weiyun Qin Jing Jiang Wenbin Bao Ming-an Sun |
| author_sort | Liangliang Zhang |
| collection | DOAJ |
| description | Alveolar macrophages (AMs) form the first defense line against various respiratory pathogens, and their immune response has a profound impact on the outcome of respiratory infection. Enhancer of zeste homolog 2 (EZH2), which catalyzes the trimethylation of H3K27 for epigenetic repression, has gained increasing attention for its immune regulation function, yet its exact function in AMs remains largely obscure. Using porcine 3D4/21 AM cells as a model, we characterized the transcriptomic and epigenomic alterations after the inhibition of EZH2. We found that the inhibition of EZH2 causes transcriptional activation of numerous immune genes and inhibits the subsequent infection by influenza A virus. Interestingly, specific families of transposable elements, particularly endogenous retrovirus elements (ERVs) and LINEs which belong to retrotransposons, also become derepressed. While some of the derepressed ERV families are pig-specific, a few ancestral families are known to be under EZH2-mediated repression in humans. Given that derepression of ERVs can promote innate immune activation through “viral mimicry”, we speculate that ERVs may also contribute to the coinciding immune activation in AMs after the inhibition of EZH2. Overall, this study improves the understanding of the EZH2-related immune regulation in AMs and provides novel insights into the epigenetic regulation of retrotransposons in pigs. |
| first_indexed | 2024-03-11T09:42:19Z |
| format | Article |
| id | doaj.art-e1b14345ec03481fa0cda86713882940 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:42:19Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e1b14345ec03481fa0cda867138829402023-11-16T16:56:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243239410.3390/ijms24032394Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar MacrophagesLiangliang Zhang0Jian Jin1Weiyun Qin2Jing Jiang3Wenbin Bao4Ming-an Sun5Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou 225009, ChinaInstitute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaAlveolar macrophages (AMs) form the first defense line against various respiratory pathogens, and their immune response has a profound impact on the outcome of respiratory infection. Enhancer of zeste homolog 2 (EZH2), which catalyzes the trimethylation of H3K27 for epigenetic repression, has gained increasing attention for its immune regulation function, yet its exact function in AMs remains largely obscure. Using porcine 3D4/21 AM cells as a model, we characterized the transcriptomic and epigenomic alterations after the inhibition of EZH2. We found that the inhibition of EZH2 causes transcriptional activation of numerous immune genes and inhibits the subsequent infection by influenza A virus. Interestingly, specific families of transposable elements, particularly endogenous retrovirus elements (ERVs) and LINEs which belong to retrotransposons, also become derepressed. While some of the derepressed ERV families are pig-specific, a few ancestral families are known to be under EZH2-mediated repression in humans. Given that derepression of ERVs can promote innate immune activation through “viral mimicry”, we speculate that ERVs may also contribute to the coinciding immune activation in AMs after the inhibition of EZH2. Overall, this study improves the understanding of the EZH2-related immune regulation in AMs and provides novel insights into the epigenetic regulation of retrotransposons in pigs.https://www.mdpi.com/1422-0067/24/3/2394alveolar macrophageEZH2porcine 3D4/21 cellinnate immunityretrotransposonendogenous retrovirus |
| spellingShingle | Liangliang Zhang Jian Jin Weiyun Qin Jing Jiang Wenbin Bao Ming-an Sun Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages International Journal of Molecular Sciences alveolar macrophage EZH2 porcine 3D4/21 cell innate immunity retrotransposon endogenous retrovirus |
| title | Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages |
| title_full | Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages |
| title_fullStr | Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages |
| title_full_unstemmed | Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages |
| title_short | Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages |
| title_sort | inhibition of ezh2 causes retrotransposon derepression and immune activation in porcine lung alveolar macrophages |
| topic | alveolar macrophage EZH2 porcine 3D4/21 cell innate immunity retrotransposon endogenous retrovirus |
| url | https://www.mdpi.com/1422-0067/24/3/2394 |
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