DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation.
Cell Mol Life Sci
; 78(19-20): 6631-6644, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-34482420
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Expressão Gênica
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Diferenciação Celular
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Regulação da Expressão Gênica
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Metilação de DNA
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Proteínas Inibidoras de Diferenciação
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Proteína 2 Inibidora de Diferenciação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Mol Life Sci
Ano de publicação:
2021
Tipo de documento:
Article