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GATAD2B regulates spindle assembly by affecting protein deacetylation during oocyte meiotic maturation

  • Qian Xu (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University) ;
  • Lina Yu (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University) ;
  • Yuling Lin (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University) ;
  • Aolei Guo (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University) ;
  • Yang Zhang (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University) ;
  • Zhe Zhang (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University) ;
  • Guijun Yan (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University) ;
  • Haixiang Sun (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University) ;
  • Guangyi Cao (State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University)
  • 투고 : 2025.01.07
  • 심사 : 2025.05.20
  • 발행 : 2025.12.01

초록

Objective: Oocyte quality is critical for the stable transmission of genetic information and affects early embryonic development. But the precise mechanisms governing oocyte meiotic progression remains largely unclear. Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and histone deacetylation (NuRD) complex. GATAD2B is known to be a component of the NuRD complex but whether GATAD2B regulates chromatin modification in mouse oocyte meiosis remains unclear. We hope to explore the role of GATAD2B in mouse oocyte meiosis. Methods: In this study, we initially utilized western blot and immunofluorescence to delineate the expression and subcellular localization of GATAD2B during oocyte meiotic maturation. To further elucidate the role of GATAD2B in regulating oocyte meiotic division, we employed the method of microinjection of Gatad2b-specific siRNA to knock down the protein expression of GATAD2B. Subsequently, dynamic changes in oocyte meiotic division were captured in real-time using live-cell imaging with Geri. Additionally, spindle staining, DNA staining, spread analysis, and reanalysis of RNA-seq data were performed to investigate the mechanisms through which GATAD2B regulates oocyte meiotic division. Results: GATAD2B was stably expressed during oocyte meiosis and was significantly increased during the metaphase II (MII) stage. To further explore the effect of GATAD2B on oocyte meiotic maturation, we observed increased abnormal spindle, severe chromosome misalignment and metaphase I (MI) block in GATAD2B knocked-down (GATAD2B-KD) oocytes. Interestingly, the distribution of microtubule organizing center was abnormal and aneuploidy was significantly increased in GATAD2B-KD oocytes. In addition, some deacetylation-related genes were significantly downregulated and acetylated proteins accumulated abnormally in GATAD2B-KD oocytes. Conclusion: These findings implicate GATAD2B as a novel regulator of histone deacetylation during oocyte maturation and provide evidence that such deacetylation is required for proper spindle assembly.

키워드

과제정보

This work was supported by the National Natural Science Foundation of China (82471691), State Key Laboratory of Reproductive Medicine and Offspring Health (SKLRM-2022D2), Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2022-LCYJ-ZD-02, 2023-LCYJ-PY-35), Research Project of Changzhou Medical Center of Nanjing Medical University, Key Program (CMCM202203), and Key Medical Research Project of Jiangsu Province Health Commission (K2023058).

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