Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos
Abstract Histone crotonylation, a conserved post-translational histone modification, plays a crucial role in transcriptional regulation. However, its function in early embryonic development remains largely unexplored. Here, we perform genome-wide mapping of histone crotonylation in mouse and human e...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60565-z |
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| author | Yong-feng Wang Yu-ting Wan Qian-rong Qi Qing Tian Xin-mei Liu Qing-zhen Xie Ying Yin Li-quan Zhou |
| author_facet | Yong-feng Wang Yu-ting Wan Qian-rong Qi Qing Tian Xin-mei Liu Qing-zhen Xie Ying Yin Li-quan Zhou |
| author_sort | Yong-feng Wang |
| collection | DOAJ |
| description | Abstract Histone crotonylation, a conserved post-translational histone modification, plays a crucial role in transcriptional regulation. However, its function in early embryonic development remains largely unexplored. Here, we perform genome-wide mapping of histone crotonylation in mouse and human early embryos. Our analysis reveals that histone crotonylation is highly enriched at promoter regions and exhibits distinct dynamic patterns throughout embryogenesis. Notably, strong histone crotonylation signals are observed at the mouse 2-cell and human 4-to-8-cell stages, coinciding with zygotic genome activation. In mice, Echs1 knockdown in oocytes, which suppresses histone crotonylation, results in developmental arrest at the 2-cell stage. Further investigation demonstrates that reduced histone crotonylation impairs transcriptional activity at zygotic genome activation genes, retrotransposon elements, and ribosomal DNA loci. Moreover, early embryos from aged female mice exhibit significantly diminished histone crotonylation, while supplementation with exogenous sodium crotonate enhances blastocyst formation. Collectively, our findings establish histone crotonylation as a key regulatory mechanism in early mammalian embryogenesis by facilitating transcriptional activation of zygotic genome activation genes and repetitive elements. |
| format | Article |
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| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-3bdca1d3acf949c3a333ee7ba7f9f2af2025-08-20T03:45:34ZengNature PortfolioNature Communications2041-17232025-07-0116112110.1038/s41467-025-60565-zEchs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryosYong-feng Wang0Yu-ting Wan1Qian-rong Qi2Qing Tian3Xin-mei Liu4Qing-zhen Xie5Ying Yin6Li-quan Zhou7Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and TechnologyCenter for Reproductive Medicine, Renmin Hospital of Wuhan UniversityDepartment of Gynecology and Obstetrics, Zhongnan Hospital of Wuhan UniversityShanghai Key Laboratory of Reproduction and DevelopmentCenter for Reproductive Medicine, Renmin Hospital of Wuhan UniversityDepartment of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Histone crotonylation, a conserved post-translational histone modification, plays a crucial role in transcriptional regulation. However, its function in early embryonic development remains largely unexplored. Here, we perform genome-wide mapping of histone crotonylation in mouse and human early embryos. Our analysis reveals that histone crotonylation is highly enriched at promoter regions and exhibits distinct dynamic patterns throughout embryogenesis. Notably, strong histone crotonylation signals are observed at the mouse 2-cell and human 4-to-8-cell stages, coinciding with zygotic genome activation. In mice, Echs1 knockdown in oocytes, which suppresses histone crotonylation, results in developmental arrest at the 2-cell stage. Further investigation demonstrates that reduced histone crotonylation impairs transcriptional activity at zygotic genome activation genes, retrotransposon elements, and ribosomal DNA loci. Moreover, early embryos from aged female mice exhibit significantly diminished histone crotonylation, while supplementation with exogenous sodium crotonate enhances blastocyst formation. Collectively, our findings establish histone crotonylation as a key regulatory mechanism in early mammalian embryogenesis by facilitating transcriptional activation of zygotic genome activation genes and repetitive elements.https://doi.org/10.1038/s41467-025-60565-z |
| spellingShingle | Yong-feng Wang Yu-ting Wan Qian-rong Qi Qing Tian Xin-mei Liu Qing-zhen Xie Ying Yin Li-quan Zhou Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos Nature Communications |
| title | Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos |
| title_full | Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos |
| title_fullStr | Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos |
| title_full_unstemmed | Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos |
| title_short | Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos |
| title_sort | echs1 mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos |
| url | https://doi.org/10.1038/s41467-025-60565-z |
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