Moyon, Sarah, Huynh, Jimmy l., Dutta, Dipankar, Zhang, Fan, Ma, Dan, Yoo, Seungyeul, Lawrence, Rebecca, Wegner, Michael, John, Gareth r., Emery, Ben, Lubetzki, Catherine, Franklin, Robin j.m., Fan, Guoping, Zhu, Jun, Dupree, Jeffrey l. and Casaccia, Patrizia (2016). Functional Characterization of DNA Methylation in the Oligodendrocyte Lineage. Cell Reports, 15 (4), pp. 748-760.
Abstract
Oligodendrocytes derive from progenitors (OPCs) through the interplay of epigenomic and transcriptional events. By integrating high-resolution methylomics, RNA-sequencing, and multiple transgenic lines, this study defines the role of DNMT1 in developmental myelination. We detected hypermethylation of genes related to cell cycle and neurogenesis during differentiation of OPCs, yet genetic ablation of Dnmt1 resulted in inefficient OPC expansion and severe hypomyelination associated with ataxia and tremors in mice. This phenotype was not caused by lineage switch or massive apoptosis but was characterized by a profound defect of differentiation associated with changes in exon-skipping and intron-retention splicing events and by the activation of an endoplasmic reticulum stress response. Therefore, loss of Dnmt1 in OPCs is not sufficient to induce a lineage switch but acts as an important determinant of the coordination between RNA splicing and protein synthesis necessary for myelin formation.
Publication DOI: | https://doi.org/10.1016/j.celrep.2016.03.060 |
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Divisions: | College of Health & Life Sciences > Aston Medical School |
Additional Information: | 2016 The Authors This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Funding: NIH-NINDS grants R37NS042925 and NS-R0152738 (P.C.) and F31NS077504 (J.L.H.), the UK Multiple Sclerosis Society (R.J.M.F.), and NIH-NIMH grant R01MH090948 (J.Z.). |
Publication ISSN: | 2211-1247 |
Last Modified: | 07 Aug 2024 07:04 |
Date Deposited: | 21 Feb 2018 08:55 |
Full Text Link: |
http://linkingh ... 21112471630331X |
Related URLs: | PURE Output Type: | Article |
Published Date: | 2016-04-14 |
Accepted Date: | 2016-03-15 |
Authors: |
Moyon, Sarah
Huynh, Jimmy l. Dutta, Dipankar Zhang, Fan Ma, Dan ( ![]() Yoo, Seungyeul Lawrence, Rebecca Wegner, Michael John, Gareth r. Emery, Ben Lubetzki, Catherine Franklin, Robin j.m. Fan, Guoping Zhu, Jun Dupree, Jeffrey l. Casaccia, Patrizia |
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