Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain

Neurosci Res. 2019 Jun:143:31-43. doi: 10.1016/j.neures.2018.05.007. Epub 2018 May 31.


Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis. Specific ablation of Np95 in adult NS/PCs (aNS/PCs) led to a decrease in their proliferation and an impairment of neuronal differentiation and to suppression of neuronal maturation associated with the impairment of dendritic formation in the hippocampal DG. We also found that deficiency of Np95 in NS/PCs increased the expression of tumor suppressor genes p16 and p53, and confirmed that expression of these genes in NS/PCs recapitulates the phenotype of Np95-deficient NS/PCs. Taken together, our findings suggest that Np95 plays an essential role in proliferation and differentiation of aNS/PCs through the regulation of tumor suppressor gene expression in adult neurogenesis.

Keywords: Adult neurogenesis; Epigenetics; Neural stem cell; Np95; UHRF1.

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism
  • Adult Stem Cells / physiology*
  • Animals
  • CCAAT-Enhancer-Binding Proteins
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Dentate Gyrus / metabolism
  • Gene Expression Regulation*
  • Genes, Tumor Suppressor*
  • Hippocampus / metabolism
  • Mice
  • Mice, Transgenic
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / physiology*
  • Neurogenesis / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Protein Ligases


  • CCAAT-Enhancer-Binding Proteins
  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Nuclear Proteins
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • Ubiquitin-Protein Ligases
  • Uhrf1 protein, mouse