N6-methyladenine demethylase ALKBH1 inhibits the differentiation of skeletal muscle.
Exp Cell Res
; 400(2): 112492, 2021 03 15.
Article
en En
| MEDLINE
| ID: mdl-33529710
ABSTRACT
DNA N6-methyladenine (N6-mA) was recently recognized as a new epigenetic modification in mammalian genome, and ALKBH1 was discovered as its demethylase. Knock-out mice studies revealed that ALKBH1 was indispensable for normal embryonic development. However, the function of ALKBH1 in myogenesis is largely unknown. In this study, we found that N6-mA showed a steady increase, going along with a strong decrease of ALKBH1 during skeletal muscle development. Our results also showed that ALKBH1 enhanced proliferation and inhibited differentiation of C2C12 cells. Genome-wide transcriptome analysis and reporter assays further revealed that ALKBH1 accomplished the differentiation inhibiting function by regulating a core set of genes and multiple signaling pathways, including increasing chemokine (C-X-C motif) ligand 14 (CXCL14) and activating ERK signaling. Taken together, our results demonstrated that ALKBH1 is critical for the myogenic differentiation of C2C12 cells, and suggested that N6-mA might be a new epigenetic mechanism for the regulation of myogenesis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adenina
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Diferenciación Celular
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Músculo Esquelético
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Desarrollo de Músculos
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Mioblastos
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Epigénesis Genética
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Histona H2a Dioxigenasa, Homólogo 1 de AlkB
Límite:
Animals
Idioma:
En
Revista:
Exp Cell Res
Año:
2021
Tipo del documento:
Article