Zfp207 is a Bub3 binding protein regulating meiotic chromosome alignment in mouse oocytes

Oncotarget. 2016 May 24;7(21):30155-65. doi: 10.18632/oncotarget.9310.

Abstract

Zinc finger proteins are a massive, diverse family of proteins that serve a wide variety of biological functions. However, the roles of them during meiosis are not yet clearly defined. Here, we report that Zfp207 localizes at the kinetochores during mouse oocyte meiotic maturation. Depletion of Zfp207 leads to a significantly higher proportion of impaired spindle organization and misaligned chromosomes in oocytes. This is coupled with the defective kinetochore-microtubule attachments, and resultantly increasing incidence of aneuploid metaphase II eggs. The precocious polar body extrusion and escape of metaphase I arrest induced by nocodazole treatment in Zfp207-depleted oocytes indicates that Zfp207 is essential for activation of SAC (Spindle Assembly Checkpoint) activity. Notably, we find that Zfp207 binds to Bub3 to form a complex and maintains its protein level in oocytes, and that overexpression of Bub3 is able to partially rescue the occurrence of aneuploid eggs in Zfp207-depleted oocytes. Collectively, we identify Zfp207 as a novel Bub3 binding protein in oocytes which plays an important role in controlling meiotic chromosome alignment and SAC function.

Keywords: K-MT attachment; Pathology Section; Zfp207; aneuploid eggs; chromosome alignment; oocyte meiosis.

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Pairing / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Knockdown Techniques
  • Kinetochores / metabolism
  • Meiosis / genetics*
  • Metaphase / genetics
  • Mice, Inbred ICR
  • Microscopy, Confocal
  • Microtubules / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Oocytes / metabolism*
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism

Substances

  • Bub3 protein, mouse
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Zfp207 protein, mouse