Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-018-04863-9
Title: PRMT5-mediated regulation of developmental myelination
Authors: Scaglione, A
Patzig, J
Liang, J
Frawley, R
Bok, J
Mela, A
Yattah, C
Zhang, J
Teo, S.X
Zhou, T
Chen, S
Bernstein, E
Canoll, P
Guccione, E 
Casaccia, P
Keywords: arginine
butyrolactone 3
gsk 591
histone deacetylase inhibitor
histone methyltransferase
lysine
nu 9056
PRMT5 protein
protein p53
unclassified drug
histone
Prmt5 protein, mouse
protein arginine methyltransferase
ablation
brucellosis
cell
inhibition
inhibitor
methylation
model validation
nervous system
protein
animal cell
animal experiment
Article
cell proliferation
controlled study
CRISPR-CAS9 system
histone acetylation
histone methylation
mouse
myelination
nonhuman
oligodendrocyte culture
oligodendrocyte precursor cell
animal
C57BL mouse
cell culture
cell differentiation
cell line
cell survival
CRISPR Cas system
cytology
gene expression profiling
genetics
HEK293 cell line
human
knockout mouse
metabolism
methylation
myelin sheath
oligodendroglia
stem cell
Mus
Animals
Cell Differentiation
Cell Line
Cell Proliferation
Cell Survival
Cells, Cultured
CRISPR-Cas Systems
Gene Expression Profiling
HEK293 Cells
Histones
Humans
Methylation
Mice, Inbred C57BL
Mice, Knockout
Myelin Sheath
Oligodendroglia
Protein-Arginine N-Methyltransferases
Stem Cells
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Scaglione, A, Patzig, J, Liang, J, Frawley, R, Bok, J, Mela, A, Yattah, C, Zhang, J, Teo, S.X, Zhou, T, Chen, S, Bernstein, E, Canoll, P, Guccione, E, Casaccia, P (2018). PRMT5-mediated regulation of developmental myelination. Nature Communications 9 (1) : 2840. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-018-04863-9
Rights: Attribution 4.0 International
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. © 2018, The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/178404
ISSN: 2041-1723
DOI: 10.1038/s41467-018-04863-9
Rights: Attribution 4.0 International
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