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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 |
Appears in Collections: | Staff Publications Elements |
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