2. Academic Validation
  3. Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function

Mettl3/Eed/Ythdc1 regulatory axis controls endometrial receptivity and function

  • Commun Biol. 2025 Feb 11;8(1):215. doi: 10.1038/s42003-025-07667-y.
Xiujuan Hu # 1,  Jincheng Li # 1,  Chenyue Ding # 1,  Jing Jiang # 1,  Wenjuan Xia # 1,  Jiafeng Lu 1,  Huapeng Su 1,  Ming Zhang 1,  Hong Li 1,  Ji-Long Liu 2,  Yuan Lin 3 4 5,  Qingxia Meng 6,  Boxian Huang 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, China.
  • 2 College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. jilongliu@scau.edu.cn.
  • 3 State Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, China. yuanlin@njmu.edu.cn.
  • 4 State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. yuanlin@njmu.edu.cn.
  • 5 Department of Maternal, Child and Adolescent Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. yuanlin@njmu.edu.cn.
  • 6 State Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, China. mqx593204@163.com.
  • 7 State Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, China. huangboxiannj@163.com.
  • # Contributed equally.
PMID: 39934221 DOI: 10.1038/s42003-025-07667-y
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.

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