PRMT5-mediated regulation of developmental myelination

Antonella Scaglione, Julia Patzig, Jialiang Liang, Rebecca Frawley, Jabez Bok, Angeliki Mela, Camila Yattah, Jingxian Zhang, Shun Xie Teo, Ting Zhou, Shuibing Chen, Emily Bernstein, Peter Canoll, Ernesto Guccione and Patrizia Casaccia ()
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Antonella Scaglione: Neuroscience Initiative at the Advanced Science Research Center of the Graduate Center of The City University of New York
Julia Patzig: Neuroscience Initiative at the Advanced Science Research Center of the Graduate Center of The City University of New York
Jialiang Liang: Icahn School of Medicine at Mount Sinai
Rebecca Frawley: Icahn School of Medicine at Mount Sinai
Jabez Bok: A*STAR (Agency for Science, Technology and Research)
Angeliki Mela: Columbia University Medical Center
Camila Yattah: Neuroscience Initiative at the Advanced Science Research Center of the Graduate Center of The City University of New York
Jingxian Zhang: A*STAR (Agency for Science, Technology and Research)
Shun Xie Teo: A*STAR (Agency for Science, Technology and Research)
Ting Zhou: Weill Cornell Medical College
Shuibing Chen: Weill Cornell Medical College
Emily Bernstein: Icahn School of Medicine at Mount Sinai
Peter Canoll: Columbia University Medical Center
Ernesto Guccione: Icahn School of Medicine at Mount Sinai
Patrizia Casaccia: Neuroscience Initiative at the Advanced Science Research Center of the Graduate Center of The City University of New York

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04863-9

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