Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function
Abstract The regulatory mechanism between N6-methyladenosine (m6A) RNA methylation and histone modification in endometrial receptivity remains poorly understood. In this study, we depict that RIF induced m6A and Mettl3 level restrain, affecting H3K27me3 modification and chromatin accessibility. We s...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07667-y |
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| author | Xiujuan Hu Jincheng Li Chenyue Ding Jing Jiang Wenjuan Xia Jiafeng Lu Huapeng Su Ming Zhang Hong Li Ji-long Liu Yuan Lin Qingxia Meng Boxian Huang |
| author_facet | Xiujuan Hu Jincheng Li Chenyue Ding Jing Jiang Wenjuan Xia Jiafeng Lu Huapeng Su Ming Zhang Hong Li Ji-long Liu Yuan Lin Qingxia Meng Boxian Huang |
| author_sort | Xiujuan Hu |
| collection | DOAJ |
| description | Abstract The regulatory mechanism between N6-methyladenosine (m6A) RNA methylation and histone modification in endometrial receptivity remains poorly understood. In this study, we depict that RIF induced m6A and Mettl3 level restrain, affecting H3K27me3 modification and chromatin accessibility. We show that Mettl3 deletion in the endometrium alters mRNA m6A methylation via Eed interaction. This reduces m6A recognized by Ythdc1, which recruits Eed to suppress H3K27me3 modification co-transcriptionally. The reduction of H3K27me3 disrupts chromatin accessibility and impairs transcription of genes critical for endometrial receptivity. Collectively, these results shed light on a Mettl3-Eed-m6A-Ythdc1 axis that links m6A and histone modification in regulating local chromatin state and gene expression, advancing our understanding of the epigenetic crosstalk between RNA and DNA modification in infertility disease. |
| format | Article |
| id | doaj-art-5d1e0ea0c0a348f9bfd7f6bbbd51b0e5 |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-5d1e0ea0c0a348f9bfd7f6bbbd51b0e52025-08-20T03:01:00ZengNature PortfolioCommunications Biology2399-36422025-02-018111410.1038/s42003-025-07667-yMettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and functionXiujuan Hu0Jincheng Li1Chenyue Ding2Jing Jiang3Wenjuan Xia4Jiafeng Lu5Huapeng Su6Ming Zhang7Hong Li8Ji-long Liu9Yuan Lin10Qingxia Meng11Boxian Huang12State Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityCollege of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityState Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical UniversityAbstract The regulatory mechanism between N6-methyladenosine (m6A) RNA methylation and histone modification in endometrial receptivity remains poorly understood. In this study, we depict that RIF induced m6A and Mettl3 level restrain, affecting H3K27me3 modification and chromatin accessibility. We show that Mettl3 deletion in the endometrium alters mRNA m6A methylation via Eed interaction. This reduces m6A recognized by Ythdc1, which recruits Eed to suppress H3K27me3 modification co-transcriptionally. The reduction of H3K27me3 disrupts chromatin accessibility and impairs transcription of genes critical for endometrial receptivity. Collectively, these results shed light on a Mettl3-Eed-m6A-Ythdc1 axis that links m6A and histone modification in regulating local chromatin state and gene expression, advancing our understanding of the epigenetic crosstalk between RNA and DNA modification in infertility disease.https://doi.org/10.1038/s42003-025-07667-y |
| spellingShingle | Xiujuan Hu Jincheng Li Chenyue Ding Jing Jiang Wenjuan Xia Jiafeng Lu Huapeng Su Ming Zhang Hong Li Ji-long Liu Yuan Lin Qingxia Meng Boxian Huang Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function Communications Biology |
| title | Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function |
| title_full | Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function |
| title_fullStr | Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function |
| title_full_unstemmed | Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function |
| title_short | Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function |
| title_sort | mettl3 eed ythdc1 regulatory axis controls endometrial receptivity and function |
| url | https://doi.org/10.1038/s42003-025-07667-y |
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