Myogenin and the SWI/SNF ATPase Brg1 maintain myogenic gene expression at different stages of skeletal myogenesis
Myogenin and the SWI/SNF ATPase Brg1 maintain myogenic gene expression at different stages of skeletal myogenesis
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DOI：
10.1074/jbc.m608898200
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发表时间：
2007-03-02
影响因子：
4.8
通讯作者：
Imbalzano, Anthony N.
中科院分区：
文献类型：
--
作者：
Ohkawa, Yasuyuki;Yoshimura, Saori;Imbalzano, Anthony N.
许多研究已经检查了骨骼肌分化起始过程中的转录调控；然而，关于成人肌肉形成和分化状态维持过程中的转录控制的信息较少。MyoD和含有Brg1 atp酶的哺乳动物SWI/SNF染色质重塑酶在细胞培养模型和发育中的胚胎组织中诱导肌肉形成是必需的，而myogenin和Brg1对于诱导终末肌肉分化的晚期基因的表达至关重要。在这里，我们证明了在胚胎肌肉发育的后期，肌原蛋白也会与它自己的启动子结合。与胚胎肌发生时的情况一样，MyoD和Brg1在初级成人肌肉卫星细胞中共定位于肌原蛋白启动子。然而，在成熟的肌纤维中，肌原蛋白和Brg1优先与肌原蛋白启动子共定位。因此，肌生成素启动子在不同的肌生成时间被不同的肌生成因子所占据。在培养中，我们证明了肌原蛋白与自身启动子持续表达的相关性，在没有MyoD的情况下，肌原蛋白能够通过招募Brg1 atp酶来修饰启动子染色质结构并促进肌原蛋白的表达。最后，我们利用体内电穿孔证明了Brg1是新生儿骨骼肌组织中肌原蛋白持续产生所必需的。这些发现有力地表明，骨骼肌表型是由肌生成素和基于brg1的SWI/SNF染色质重塑酶的持续活性维持的。
Many studies have examined transcriptional regulation during the initiation of skeletal muscle differentiation; however, there is less information regarding transcriptional control during adult myogenesis and during the maintenance of the differentiated state. MyoD and the mammalian SWI/SNF chromatinremodeling enzymes containing the Brg1 ATPase are necessary to induce myogenesis in cell culture models and in developing embryonic tissue, whereas myogenin and Brg1 are critical for the expression of the late genes that induce terminal muscle differentiation. Here, we demonstrate that myogenin also binds to its own promoter during the late stages of embryonic muscle development. As is the case during embryonic myogenesis, MyoD and Brg1 co-localize to the myogenin promoter in primary adult muscle satellite cells. However, in mature myofibers, myogenin and Brg1 are preferentially co-localized to the myogenin promoter. Thus, the myogenin promoter is occupied by different myogenic factors at different times of myogenesis. The relevance of myogenin in the continued expression from its own promoter is demonstrated in culture, where we show that myogenin, in the absence of MyoD, is capable of maintaining its own expression by recruiting the Brg1 ATPase to modify promoter chromatin structure and facilitate myogenin expression. Finally, we utilized in vivo electroporation to demonstrate that Brg1 is required for the continued production of the myogenin protein in newborn skeletal muscle tissue. These findings strongly suggest that the skeletal muscle phenotype is maintained by myogenin and the continuous activity of Brg1-based SWI/SNF chromatin-remodeling enzymes.