Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3
Abstract Mitofusin 1 (MFN1) plays a crucial role in mitochondrial fusion and oocyte development. However, its function in preimplantation embryonic development and its potential involvement in epigenetic regulation remain poorly understood. In this study, it is shown that MFN1 interacts with PADI6,...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202414985 |
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| author | Xiao‐yan Shi Yu Tian Yu‐fan Wang Yi‐ran Zhang Ying Yin Qing Tian Lei Li Bing‐xin Ma Ximiao He Li‐quan Zhou |
| author_facet | Xiao‐yan Shi Yu Tian Yu‐fan Wang Yi‐ran Zhang Ying Yin Qing Tian Lei Li Bing‐xin Ma Ximiao He Li‐quan Zhou |
| author_sort | Xiao‐yan Shi |
| collection | DOAJ |
| description | Abstract Mitofusin 1 (MFN1) plays a crucial role in mitochondrial fusion and oocyte development. However, its function in preimplantation embryonic development and its potential involvement in epigenetic regulation remain poorly understood. In this study, it is shown that MFN1 interacts with PADI6, a key component of the cytoplasmic lattice in oocytes and early embryos. MFN1 deficiency in mice results in reduced PADI6 levels and decreased expression of translational machinery components, which suppress protein synthesis activity and lower histone H3.3 abundance. These disruptions lead to the failure of male pronucleus formation, aberrant zygotic genome activation, and impaired embryonic development. It is further demonstrated that the MFN1 activator S89 promotes H3.3 incorporation and rescues early development in maternally aged embryos with low MFN1 levels. Additionally, a positive correlation between MFN1 and H3.3 protein levels in early human embryos is observed. Together, these findings provide new insights into MFN1's role in regulating epigenetic reprogramming during preimplantation embryo development. |
| format | Article |
| id | doaj-art-140a7b41491f4378bbd01c67105b49cf |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-140a7b41491f4378bbd01c67105b49cf2025-08-20T02:34:47ZengWileyAdvanced Science2198-38442025-05-011218n/an/a10.1002/advs.202414985Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3Xiao‐yan Shi0Yu Tian1Yu‐fan Wang2Yi‐ran Zhang3Ying Yin4Qing Tian5Lei Li6Bing‐xin Ma7Ximiao He8Li‐quan Zhou9Institute of Reproductive Health Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 ChinaInstitute of Reproductive Health Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 ChinaInstitute of Reproductive Health Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 ChinaInstitute of Reproductive Health Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 ChinaDepartment of Physiology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 ChinaDepartment of Gynecology and Obstetrics Zhongnan Hospital of Wuhan University Wuhan Hubei 430071 ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaReproductive Medicine Center Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 P. R. ChinaDepartment of Physiology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 ChinaInstitute of Reproductive Health Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 ChinaAbstract Mitofusin 1 (MFN1) plays a crucial role in mitochondrial fusion and oocyte development. However, its function in preimplantation embryonic development and its potential involvement in epigenetic regulation remain poorly understood. In this study, it is shown that MFN1 interacts with PADI6, a key component of the cytoplasmic lattice in oocytes and early embryos. MFN1 deficiency in mice results in reduced PADI6 levels and decreased expression of translational machinery components, which suppress protein synthesis activity and lower histone H3.3 abundance. These disruptions lead to the failure of male pronucleus formation, aberrant zygotic genome activation, and impaired embryonic development. It is further demonstrated that the MFN1 activator S89 promotes H3.3 incorporation and rescues early development in maternally aged embryos with low MFN1 levels. Additionally, a positive correlation between MFN1 and H3.3 protein levels in early human embryos is observed. Together, these findings provide new insights into MFN1's role in regulating epigenetic reprogramming during preimplantation embryo development.https://doi.org/10.1002/advs.202414985cytoplasmic latticeH3.3MFN1preimplantationzygotic genome activation |
| spellingShingle | Xiao‐yan Shi Yu Tian Yu‐fan Wang Yi‐ran Zhang Ying Yin Qing Tian Lei Li Bing‐xin Ma Ximiao He Li‐quan Zhou Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3 Advanced Science cytoplasmic lattice H3.3 MFN1 preimplantation zygotic genome activation |
| title | Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3 |
| title_full | Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3 |
| title_fullStr | Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3 |
| title_full_unstemmed | Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3 |
| title_short | Mitofusin 1 Drives Preimplantation Development by Enhancing Chromatin Incorporation of Histone H3.3 |
| title_sort | mitofusin 1 drives preimplantation development by enhancing chromatin incorporation of histone h3 3 |
| topic | cytoplasmic lattice H3.3 MFN1 preimplantation zygotic genome activation |
| url | https://doi.org/10.1002/advs.202414985 |
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