title: Type II arginine methyltransferase PRMT5 regulates gene expression of inhibitors of differentiation/DNA binding Id2 and Id4 during glial cell differentiation.
abstract: PRMT5 is a type II protein arginine methyltranferase that catalyzes monomethylation and symmetric dimethylation of arginine residues. PRMT5 is functionally involved in a variety of biological processes including embryo development and circadian clock regulation. However, the role of PRMT5 in oligodendrocyte differentiation and central nervous system myelination is unknown. Here we show that PRMT5 expression gradually increases throughout postnatal brain development, coinciding with the period of active myelination. PRMT5 expression was observed in neurons, astrocytes, and oligodendrocytes. siRNA-mediated depletion of PRMT5 in mouse primary oligodendrocyte progenitor cells abrogated oligodendrocyte differentiation. In addition, the PRMT5-depleted oligodendrocyte progenitor and C6 glioma cells expressed high levels of the inhibitors of differentiation/DNA binding, Id2 and Id4, known repressors of glial cell differentiation. We observed that CpG-rich islands within the Id2 and Id4 genes were bound by PRMT5 and were hypomethylated in PRMT5-deficient cells, suggesting that PRMT5 plays a role in gene silencing during glial cell differentiation. Our findings define a role of PRMT5 in glial cell differentiation and link PRMT5 to epigenetic changes during oligodendrocyte differentiation.
authors: Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Montréal, Québec H3T 1E2, Canada.
authors: Jinghan
authors: J
authors: Huang
authors: Gillian
authors: G
authors: Vogel
authors: Zhenbao
authors: Z
authors: Yu
authors: Guillermina
authors: G
authors: Almazan
authors: Stéphane
authors: S
authors: Richard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000502:physiology; D020868:Gene Silencing / Q000502:physiology*; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis* / Q000235:genetics; D008745:Methylation; D051379:Mice; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C497451:Id2 protein, rat; C490126:Id4 protein, rat; C497452:Idb2 protein, mouse; C086479:Idb4 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D009419:Nerve Tissue Proteins; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases