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Title: | DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation | Authors: | TIANE, Assia SCHEPERS, Melissa Riemens, Renzo ROMBAUT, Ben VANDORMAEL, Patrick SOMERS, Veerle Prickaerts, Jos HELLINGS, Niels van den Hove, Daniel VANMIERLO, Tim |
Issue Date: | 2021 | Publisher: | SPRINGER BASEL AG | Source: | Cellular and Molecular Life Sciences, 17 (19-20), p. 6631-6644 | Abstract: | The differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes is the prerequisite for remyelination in demyelinated disorders such as multiple sclerosis (MS). Epigenetic mechanisms, such as DNA methylation, have been suggested to control the intricate network of transcription factors involved in OPC differentiation. Yet, the exact mechanism remains undisclosed. Here, we are the first to identify the DNA-binding protein inhibitors, Id2 and Id4, as targets of DNA methylation during OPC differentiation. Using state-of-the-art epigenetic editing via CRISPR/dCas9-DNMT3a, we confirm that targeted methylation of Id2/Id4 drives OPC differentiation. Moreover, we show that in the pathological context of MS, methylation and gene expression levels of both ID2 and ID4 are altered compared to control human brain samples. We conclude that DNA methylation is crucial to suppress ID2 and ID4 during OPC differentiation, a process that appears to be dysregulated during MS. Our data do not only reveal new insights into oligodendrocyte biology, but could also lead to a better understanding of CNS myelin disorders. | Notes: | Vanmierlo, T (corresponding author), Hasselt Univ, Fac Med & Life Sci, Biomed Res Inst, Dept Neurosci, Hasselt, Belgium.; Vanmierlo, T (corresponding author), Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands.; Vanmierlo, T (corresponding author), Univ MS Ctr UMSC Hasselt Pelt, Hasselt, Belgium. assia.tiane@uhasselt.be; melissa.schepers@uhasselt.be; renzo.riemens@maastrichtuniversity.nl; ben.rombaut@uhasselt.be; patrick.vandormael@uhasselt.be; veerle.somers@uhasselt.be; jos.prickaerts@maastrichtuniversity.nl; niels.hellings@uhasselt.be; d.vandenhove@maastrichtuniversity.nl; tim.vanmierlo@uhasselt.be |
Keywords: | Oligodendrocyte;Oligodendrocyte precursor cell;Methylation;Myelination;ID2;ID4 | Document URI: | http://hdl.handle.net/1942/35758 | ISSN: | 1420-682X | e-ISSN: | 1420-9071 | DOI: | 10.1007/s00018-021-03927-2 | ISI #: | WOS:000698181700001 | Rights: | The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
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Tiane2021_Article_DNAMethylationRegulatesTheExpr.pdf | Published version | 2.89 MB | Adobe PDF | View/Open |
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