PRMT5-mediated regulation of developmental myelination

Nature Communications
Antonella ScaglionePatrizia Casaccia

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.

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Sep 17, 2018·Journal of Biochemistry·Koichiro KakoAkiyoshi Fukamizu
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Datasets Mentioned

BETA
GSE94067

Methods Mentioned

BETA
acetylation
Peptide Array
histone acetylation
acetylate
transfection
electrophoresis
PCR
affinity
gel filtration
size-exclusion chromatography

Software Mentioned

Cuffdiff
ImageJ
MATS
array analyzer
ENSEMBL
Bowtie
Ensemble
R
Active Motif
GSEA

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