Ezh1 regulates expression of Cpg15/Neuritin in mouse cortical neurons

Drug Discov Ther. 2021 May 11;15(2):55-65. doi: 10.5582/ddt.2021.01017. Epub 2021 Mar 8.

Abstract

Immature neurons undergo morphological and physiological maturation in order to establish neuronal networks. During neuronal maturation, a large number of genes change their transcriptional levels, and these changes may be mediated by chromatin modifiers. In this study, we found that the level of Ezh1, a component of Polycomb repressive complex 2 (PRC2), increases during neuronal maturation in mouse neocortical culture. In addition, conditional knockout of Ezh1 in post-mitotic excitatory neurons leads to downregulation of a set of genes related to neuronal maturation. Moreover, the locus encoding Cpg15/Neuritin (Nrn1), which is regulated by neuronal activity and implicated in stabilization and maturation of excitatory synapses, is a direct target of Ezh1 in cortical neurons. Together, these results suggest that elevated expression of Ezh1 contributes to maturation of cortical neurons.

Keywords: Alzheimer's disease; Nrn1; Polycomb group proteins; depression; epigenetics; neuronal maturation.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Animals
  • Cerebral Cortex / cytology
  • Depression / genetics
  • Depression / metabolism
  • Down-Regulation
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / genetics
  • Neurons / metabolism*
  • Neurons / physiology
  • Polycomb Repressive Complex 2 / blood
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*

Substances

  • GPI-Linked Proteins
  • Nerve Tissue Proteins
  • Nrn1 protein, mouse
  • Ezh1 protein, mouse
  • Polycomb Repressive Complex 2