Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic satellite cells.

Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic satellite cells.
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DOI:
10.1083/jcb.200904144
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发表时间:
2010-01-11
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Harter ML
Harter ML
中科院分区:
其他
文献类型:
--
作者:
Zhang K;Sha J;Harter ML

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Cdc6 可以改变染色质超微结构,从而允许肌肉干细胞中的 DNA 复制从静止状态转变出来,它被确定为 MyoD 转录因子的靶标。 MyoD 是肌肉干细胞(卫星细胞)分化所需的转录因子。在这项研究中,我们描述了 MyoD 在调节基因 (Cdc6) 方面的一种先前未知的功能,该基因对于赋予染色质复制 DNA 的能力至关重要。在 C2C12 和原代小鼠成肌细胞中,我们发现 MyoD 可以占据 Cdc6 启动子内的 E-box,并且这种关联与 E2F3a 是其活性所必需的。 MyoD 和 Cdc6 均在静态 C2C12 成肌细胞或与肌纤维相关的卫星细胞受到刺激生长后表达,但 MyoD 比 Cdc6 至少早 2-3 小时出现。最后,MyoD 的敲低会损害 C2C12 细胞在离开静止状态后表达 Cdc6 的能力,从而导致它们无法完全进入 S 期。我们的结果定义了一种机制,MyoD 可以通过该机制帮助肌源性卫星细胞在脱离静止状态后进入第一轮 DNA 复制。
Cdc6, which alters chromatin ultrastructure to allow DNA replication in muscle stem cells transitioning out of quiescence, is identified as a target of the MyoD transcription factor. MyoD is a transcriptional factor that is required for the differentiation of muscle stem cells (satellite cells). In this study, we describe a previously unknown function for MyoD in regulating a gene (Cdc6) that is vital to endowing chromatin with the capability of replicating DNA. In C2C12 and primary mouse myoblasts, we show that MyoD can occupy an E-box within the promoter of Cdc6 and that this association, along with E2F3a, is required for its activity. MyoD and Cdc6 are both expressed after quiescent C2C12 myoblasts or satellite cells in association with myofibers are stimulated for growth, but MyoD appears at least 2–3 h earlier than Cdc6. Finally, knockdown of MyoD impairs the ability of C2C12 cells to express Cdc6 after leaving quiescence, and as a result, they cannot fully progress into S phase. Our results define a mechanism by which MyoD helps myogenic satellite cells to enter into the first round of DNA replication after transitioning out of quiescence.
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