title: RBBP4 regulates histone deacetylation and bipolar spindle assembly during oocyte maturation in the mouse.
abstract: During meiosis I (MI) in oocytes, the maturation-associated decrease of histone acetylation is critical for normal meiotic progression and accurate chromosome segregation. RBBP4 is a component of several different histone deacetylase containing chromatin-remodeling complexes, but RBBP4's role in regulating MI is not known. Depleting RBBP4 in mouse oocytes resulted in multipolar spindles at metaphase (Met) I with subsequent perturbed meiotic progression and increased incidence of abnormal spindles, chromosome misalignment, and aneuploidy at Met II. We attribute these defects to improper deacetylation of histones because histones H3K4, H4K8, H4K12, and H4K16 were hyperacetylated in RBBP4-depleted oocytes. Importantly, we show that RBBP4-mediated histone deacetylation is essential for regulating bipolar spindle assembly, at least partially, through promoting Aurora kinase (AURK) C function. To our knowledge, these results are the first to identify RBBP4 as a regulator of histone deacetylation during oocyte maturation, and they provide evidence that deacetylation is required for bipolar spindle assembly through AURKC.
authors: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, New Jersey Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania Theriogenology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
authors: Ahmed Z
authors: AZ
authors: Balboula
authors: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Paula
authors: P
authors: Stein
authors: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania rschultz@sas.upenn.edu.
authors: Richard M
authors: RM
authors: Schultz
authors: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, New Jersey schindler@biology.rutgers.edu.
authors: Karen
authors: K
authors: Schindler
mesh_terms: D000818:Animals; D064108:Aurora Kinase C / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics; D047108:Embryonic Development; D005260:Female; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000378:metabolism*; D008540:Meiosis / Q000235:genetics / Q000502:physiology; D051379:Mice; D009865:Oocytes / Q000502:physiology*; D011247:Pregnancy; D056505:Retinoblastoma-Binding Protein 4 / Q000235:genetics / Q000502:physiology*; D056524:Retinoblastoma-Binding Protein 7 / Q000235:genetics / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology*
chemical_list: C489969:Rbbp4 protein, mouse; C096378:Rbbp7 protein, mouse; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D064108:Aurora Kinase C; D006655:Histone Deacetylases
keywords: Aurora kinase; RBBP4; chromatin; histone; histone deacetylation; meiotic maturation; meiotic spindle; oocyte; oocyte maturation; spindle