MiR-203 Interplays with Polycomb Repressive Complexes to Regulate the Proliferation of Neural Stem/Progenitor Cells

Stem Cell Reports. 2017 Jul 11;9(1):190-202. doi: 10.1016/j.stemcr.2017.05.007. Epub 2017 Jun 8.

Abstract

The polycomb repressive complexes 1 (PRC1) and 2 (PRC2) are two distinct polycomb group (PcG) proteins that maintain the stable silencing of specific sets of genes through chromatin modifications. Although the PRC2 component EZH2 has been known as an epigenetic regulator in promoting the proliferation of neural stem/progenitor cells (NSPCs), the regulatory network that controls this process remains largely unknown. Here we show that miR-203 is repressed by EZH2 in both embryonic and adult NSPCs. MiR-203 negatively regulates the proliferation of NSPCs. One of PRC1 components, Bmi1, is a downstream target of miR-203 in NSPCs. Conditional knockout of Ezh2 results in decreased proliferation ability of both embryonic and adult NSPCs. Meanwhile, ectopic overexpression of BMI1 rescues the proliferation defects exhibited by miR-203 overexpression or EZH2 deficiency in NSPCs. Therefore, this study provides evidence for coordinated function of the EZH2-miR-203-BMI1 regulatory axis that regulates the proliferation of NSPCs.

Keywords: BMI1; Ezh2; PRC1; PRC2; miR-203; neural stem/progenitor cells; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation*
  • Cells, Cultured
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Epigenesis, Genetic
  • Gene Deletion
  • Gene Expression Regulation, Developmental*
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis
  • Polycomb Repressive Complex 1 / genetics*
  • Proto-Oncogene Proteins / genetics*

Substances

  • Bmi1 protein, mouse
  • MIRN203 microRNA, mouse
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • Polycomb Repressive Complex 1