METHYLATION AND EXPRESSION OF THE MYO-D1 DETERMINATION GENE

METHYLATION AND EXPRESSION OF THE MYO-D1 DETERMINATION GENE
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DOI:
10.1098/rstb.1990.0011
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发表时间:
1990-01-30
影响因子:
6.3
通讯作者:
GONZALES, F
GONZALES, F
中科院分区:
生物学1区
文献类型:
--
作者:
JONES, PA;WOLKOWICZ, MJ;GONZALES, F

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与脱甲基剂5-氮杂丁胺分化的小鼠胚胎细胞代表了研究发育分子控制的出色模型系统。在药物治疗后,可以从多能级亲属系中分离出已确定为肌原性或成脂谱系的10T1/2细胞的克隆衍生物。这些确定的衍生物可以无限期地培养,并在适当刺激的情况下区分为终阶段表型。最近从这种成肌细胞系中分离出的一个称为Myo D1的基因将在10T1/2或其他细胞类型中表达时赋予肌发生(Davis等,1987)。 Myo D1的cDNA包含大量的CpG序列,并且该基因在10T1/2细胞中相对甲基化和脂肪细胞衍生物,但在肌源性衍生物中被脱甲基化。因此,Myo D1可以在体外受到甲基化控制。另一方面,初步观察表明,在体内CCGG部位未甲基化Myo D1,因此在体外可能发生了从头甲基化事件。这些观察结果可能在建立不朽的细胞系和肿瘤中具有重要意义。
Mouse embryo cells induced to differentiate with the demethylating agent 5-azacytidine represent an excellent model system to investigate the molecular control of development. Clonal derivatives of 10T1/2 cells that have become determined to the myogenic or adipogenic lineages can be isolated from the multipotential parental line after drug treatment. These determined derivatives can be cultured indefinitely and will differentiate into end-stage phenotypes on appropriate stimulation. A gene called Myo D1, recently isolated from such a myoblast line, will confer myogenesis when expressed in 10T1/2 or other cell types (Davis et al. 1987). The cDNA for Myo D1 contains a large number of CpG sequences and the gene is relatively methylated in 10T1/2 cells and an adipocyte derivative, but is demethylated in myogenic derivatives. Myo D1 may therefore be subject to methylation control in vitro. On the other hand, preliminary observations suggest that Myo D1 is not methylated at CCGG sites in vivo so that a de novo methylation event may have occurred in vitro. These observations may have significance in the establishment of immortal cell lines and tumours.