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Knockdown of RBBP7 unveils a requirement of histone deacetylation for CPC function in mouse oocytes
Ahmed Z Balboula1, Paula Stein2, Richard M Schultz2
1Department of Genetics; Rutgers; The State University of New Jersey; Piscataway, NJ USA; Department of Biology; University of Pennsylvania; Philadelphia, PA USA; Theriogenology Department; Faculty of Veterinary Medicine; Mansoura University; Mansoura, Egypt.
Abstract:
During mouse oocyte maturation histones are deacetylated, and inhibiting this deacetylation leads to abnormal chromosome segregation and aneuploidy. RBBP7 is a component of several different complexes that contain histone deacetylases, and therefore could be implicated in histone deacetylation. We find that Rbbp7 is a dormant maternal mRNA that is recruited for translation during oocyte maturation to regulate the histone deacetylation. Importantly, we show that the maturation-associated decrease of histone acetylation is required for localization and function of the chromosomal passenger complex (CPC) during oocyte meiotic maturation. This finding can explain the phenotypes of oocytes where Rbbp7 is depleted by an siRNA/morpholino cocktail including severe chromosome misalignment, improper kinetochore-microtubule attachments, impaired SAC function, cytokinesis defects, and increased incidence of aneuploidy at metaphase II (Met II). These results implicate RBBP7 as a novel regulator of histone deacetylation during oocyte maturation and provide evidence that such deacetylation is required for proper chromosome segregation by regulating localized CPC function.
Insights
RBBP7 regulates histone deacetylation during oocyte maturation, which is crucial for proper chromosome segregation. Depleting RBBP7 causes aneuploidy and defects in chromosomal passenger complex function.
Area of Science:
- Reproductive biology
- Molecular and cell biology
- Epigenetics
Background:
- Histone deacetylation is essential for mouse oocyte maturation and preventing aneuploidy.
- RBBP7, a component of histone deacetylase complexes, may play a role in this process.
Purpose of the Study:
- To investigate the role of RBBP7 in histone deacetylation during oocyte maturation.
- To determine the impact of RBBP7 depletion on chromosome segregation and related processes.
Main Methods:
- Utilized siRNA/morpholino to deplete RBBP7 in mouse oocytes.
- Assessed histone acetylation levels, chromosomal passenger complex (CPC) localization and function, and chromosome segregation fidelity.
- Analyzed oocyte maturation, kinetochore-microtubule attachments, spindle assembly checkpoint (SAC) function, and cytokinesis.
Main Results:
- RBBP7 is translated from dormant maternal mRNA during oocyte maturation to regulate histone deacetylation.
- Maturation-associated histone deacetylation is required for proper CPC localization and function.
- RBBP7 depletion leads to chromosome misalignment, impaired kinetochore-microtubule attachments, defective SAC function, cytokinesis issues, and increased aneuploidy.
Conclusions:
- RBBP7 is a novel regulator of histone deacetylation essential for oocyte maturation.
- Histone deacetylation, mediated by RBBP7, is critical for accurate chromosome segregation via localized CPC function during meiosis.
