Knockdown of RBBP7 unveils a requirement of histone deacetylation for CPC function in mouse oocytes

Cell Cycle. 2014;13(4):600-11. doi: 10.4161/cc.27410. Epub 2013 Dec 6.

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.

Keywords: Aurora kinase; CPC; RBBP7; aneuploidy; histone deacetylation; mouse oocyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Aurora Kinase B / metabolism*
  • Aurora Kinase C / genetics
  • Aurora Kinase C / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation
  • Female
  • Gene Knockdown Techniques
  • Histones / metabolism*
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Meiosis
  • Mice
  • Multiprotein Complexes / metabolism
  • Oocytes / cytology
  • Oocytes / metabolism*
  • RNA, Small Interfering / genetics
  • Repressor Proteins / metabolism*
  • Retinoblastoma-Binding Protein 7 / genetics*
  • Retinoblastoma-Binding Protein 7 / metabolism
  • Survivin

Substances

  • Birc5 protein, mouse
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Incenp protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Multiprotein Complexes
  • RNA, Small Interfering
  • Rbbp7 protein, mouse
  • Repressor Proteins
  • Retinoblastoma-Binding Protein 7
  • Survivin
  • Aurora Kinase B
  • Aurora Kinase C