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DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation

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 tra...

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Autores principales: Tiane, Assia, Schepers, Melissa, Riemens, Renzo, Rombaut, Ben, Vandormael, Patrick, Somers, Veerle, Prickaerts, Jos, Hellings, Niels, van den Hove, Daniel, Vanmierlo, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558293/
https://www.ncbi.nlm.nih.gov/pubmed/34482420
http://dx.doi.org/10.1007/s00018-021-03927-2
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author Tiane, Assia
Schepers, Melissa
Riemens, Renzo
Rombaut, Ben
Vandormael, Patrick
Somers, Veerle
Prickaerts, Jos
Hellings, Niels
van den Hove, Daniel
Vanmierlo, Tim
author_facet Tiane, Assia
Schepers, Melissa
Riemens, Renzo
Rombaut, Ben
Vandormael, Patrick
Somers, Veerle
Prickaerts, Jos
Hellings, Niels
van den Hove, Daniel
Vanmierlo, Tim
author_sort Tiane, Assia
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-03927-2.
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spelling pubmed-85582932021-11-15 DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation Tiane, Assia Schepers, Melissa Riemens, Renzo Rombaut, Ben Vandormael, Patrick Somers, Veerle Prickaerts, Jos Hellings, Niels van den Hove, Daniel Vanmierlo, Tim Cell Mol Life Sci Original Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-021-03927-2. Springer International Publishing 2021-09-05 2021 /pmc/articles/PMC8558293/ /pubmed/34482420 http://dx.doi.org/10.1007/s00018-021-03927-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Tiane, Assia
Schepers, Melissa
Riemens, Renzo
Rombaut, Ben
Vandormael, Patrick
Somers, Veerle
Prickaerts, Jos
Hellings, Niels
van den Hove, Daniel
Vanmierlo, Tim
DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation
title DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation
title_full DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation
title_fullStr DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation
title_full_unstemmed DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation
title_short DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation
title_sort dna methylation regulates the expression of the negative transcriptional regulators id2 and id4 during opc differentiation
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558293/
https://www.ncbi.nlm.nih.gov/pubmed/34482420
http://dx.doi.org/10.1007/s00018-021-03927-2
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