First Author | Diao LT | Year | 2021 |
Journal | Exp Cell Res | Volume | 400 |
Issue | 2 | Pages | 112492 |
PubMed ID | 33529710 | Mgi Jnum | J:306273 |
Mgi Id | MGI:6707034 | Doi | 10.1016/j.yexcr.2021.112492 |
Citation | Diao LT, et al. (2021) N(6)-methyladenine demethylase ALKBH1 inhibits the differentiation of skeletal muscle. Exp Cell Res 400(2):112492 |
abstractText | DNA N(6)-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. |