PRMT5-mediated regulation of developmental myelination. Academic Article uri icon

Overview

abstract

  • Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system. They are derived from differentiation of oligodendrocyte progenitors through a process requiring cell cycle exit and histone modifications. Here we identify the histone arginine methyl-transferase PRMT5, a molecule catalyzing symmetric methylation of histone H4R3, as critical for developmental myelination. PRMT5 pharmacological inhibition, CRISPR/cas9 targeting, or genetic ablation decrease p53-dependent survival and impair differentiation without affecting proliferation. Conditional ablation of Prmt5 in progenitors results in hypomyelination, reduced survival and differentiation. Decreased histone H4R3 symmetric methylation is followed by increased nuclear acetylation of H4K5, and is rescued by pharmacological inhibition of histone acetyltransferases. Data obtained using purified histones further validate the results obtained in mice and in cultured oligodendrocyte progenitors. Together, these results identify PRMT5 as critical for oligodendrocyte differentiation and developmental myelination by modulating the cross-talk between histone arginine methylation and lysine acetylation.

publication date

  • July 19, 2018

Research

keywords

  • Myelin Sheath
  • Oligodendroglia
  • Protein-Arginine N-Methyltransferases
  • Stem Cells

Identity

PubMed Central ID

  • PMC6053423

Scopus Document Identifier

  • 85050612507

Digital Object Identifier (DOI)

  • 10.1006/jmbi.1997.1235

PubMed ID

  • 30026560

Additional Document Info

volume

  • 9

issue

  • 1