ING3 is essential for asymmetric cell division during mouse oocyte maturation

PLoS One. 2013 Sep 16;8(9):e74749. doi: 10.1371/journal.pone.0074749. eCollection 2013.

Abstract

ING3 (inhibitor of growth family, member 3) is a subunit of the nucleosome acetyltransferase of histone 4 (NuA4) complex, which activates gene expression. ING3, which contains a plant homeodomain (PHD) motif that can bind to trimethylated lysine 4 on histone H3 (H3K4me3), is ubiquitously expressed in mammalian tissues and governs transcriptional regulation, cell cycle control, and apoptosis via p53-mediated transcription or the Fas/caspase-8 pathway. Thus, ING3 plays a number of important roles in various somatic cells. However, the role(s) of ING3 in germ cells remains unknown. Here, we show that loss of ING3 function led to the failure of asymmetric cell division and cortical reorganization in the mouse oocyte. Immunostaining showed that in fully grown germinal vesicle (GV) oocytes, ING3 localized predominantly in the GV. After germinal vesicle breakdown (GVBD), ING3 homogeneously localized in the cytoplasm. In oocytes where Ing3 was targeted by siRNA microinjection, we observed symmetric cell division during mouse oocyte maturation. In those oocytes, oocyte polarization was not established due to the failure to form an actin cap or a cortical granule-free domain (CGFD), the lack of which inhibited spindle migration. These features were among the main causes of abnormal symmetric cell division. Interestingly, an analysis of the mRNA expression levels of genes related to asymmetric cell division revealed that only mTOR was downregulated, and, furthermore, that genes downstream of mTOR (e.g., Cdc42, Rac1, and RhoA) were also downregulated in siIng3-injected oocytes. Therefore, ING3 may regulate asymmetric cell division through the mTOR pathway during mouse oocyte maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asymmetric Cell Division / genetics
  • Asymmetric Cell Division / physiology*
  • Cells, Cultured
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Oocytes / cytology*
  • Oocytes / metabolism*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Homeodomain Proteins
  • TOR Serine-Threonine Kinases

Grants and funding

This work was supported in part by a grant from the Ministry of Education, Science and Culture to N.M. (grant 23380164). No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.