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Related Experiment Video

Updated: May 28, 2025

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

Xiujuan Hu1, Jincheng Li1, Chenyue Ding1

  • 1State 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.

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|February 11, 2025
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This study reveals how N6-methyladenosine (m6A) RNA methylation and histone modification impact endometrial receptivity. It identifies a Mettl3-Eed-Ythdc1 pathway crucial for regulating gene expression and chromatin state in infertility.

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Area of Science:

  • Epigenetics
  • Molecular Biology
  • Reproductive Biology

Background:

  • The interplay between RNA methylation (m6A) and histone modifications in regulating endometrial receptivity is not well understood.
  • Endometrial receptivity is crucial for successful implantation and pregnancy, and its dysregulation can lead to infertility.

Purpose of the Study:

  • To elucidate the regulatory mechanism linking m6A RNA methylation and histone modification in endometrial receptivity.
  • To investigate the role of Mettl3, Eed, and Ythdc1 in this process and their impact on chromatin accessibility and gene expression.

Main Methods:

  • Utilized knockout models (Mettl3 deletion in the endometrium) to study the effects on m6A methylation and histone modifications.
  • Investigated the interaction between Mettl3 and Eed and its influence on H3K27me3 suppression.
  • Analyzed the recruitment of Ythdc1 and its role in recognizing m6A-modified RNA to regulate gene transcription.

Main Results:

  • RIF induction led to decreased m6A and Mettl3 levels, impacting H3K27me3 modification and chromatin accessibility.
  • Mettl3 deletion in the endometrium altered mRNA m6A methylation through Eed interaction, reducing Ythdc1-mediated suppression of H3K27me3.
  • Reduced H3K27me3 resulted in disrupted chromatin accessibility and impaired transcription of key genes for endometrial receptivity.

Conclusions:

  • Identified a novel Mettl3-Eed-m6A-Ythdc1 axis that connects m6A RNA methylation and histone modification.
  • This axis regulates local chromatin state and gene expression, offering insights into the epigenetic crosstalk between RNA and DNA modifications.
  • The findings advance the understanding of epigenetic mechanisms underlying infertility and may provide therapeutic targets.