Skeletal muscle specification by myogenin and Mef2D via the SWI/SNF ATPase Brg1
Skeletal muscle specification by myogenin and Mef2D via the SWI/SNF ATPase Brg1
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DOI：
10.1038/sj.emboj.7600943
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发表时间：
2006-02-08
期刊：
影响因子：
11.4
通讯作者：
Imbalzano, AN
中科院分区：
文献类型：
--
作者：
Ohkawa, Y;Marfella, CGA;Imbalzano, AN
肌细胞生成素不是肌细胞生成的起始所必需的，而是通过知之甚少的机制用于骨骼肌形成。我们证明在培养的细胞中，并首次在胚胎组织中，指定骨骼肌表型的生肌晚期基因在基因表达开始之前被MyoD结合。在肌肉规格的开始，从MyoD肌细胞生成素的过渡发生在晚期基因位点，伴随着HDAC2的损失，Mef2D调节剂和Brg1染色质重塑酶的出现，以及染色质结构的开放。我们进一步证明，在MyoD不存在的情况下，肌细胞生成素和Mef2D的异位表达足以以完全依赖于Brg1的方式诱导肌肉分化。这些结果表明，肌细胞生成素指定的肌肉表型与Mef2D合作，招募ATP依赖性染色质重塑酶，改变染色质结构的调控序列，以促进终末分化。
Myogenin is required not for the initiation of myogenesis but instead for skeletal muscle formation through poorly understood mechanisms. We demonstrate in cultured cells and, for the first time, in embryonic tissue, that myogenic late genes that specify the skeletal muscle phenotype are bound by MyoD prior to the initiation of gene expression. At the onset of muscle specification, a transition from MyoD to myogenin occurred at late gene loci, concomitant with loss of HDAC2, the appearance of both the Mef2D regulator and the Brg1 chromatin-remodeling enzyme, and the opening of chromatin structure. We further demonstrated that ectopic expression of myogenin and Mef2D, in the absence of MyoD, was sufficient to induce muscle differentiation in a manner entirely dependent on Brg1. These results indicate that myogenin specifies the muscle phenotype by cooperating with Mef2D to recruit an ATP-dependent chromatin-remodeling enzyme that alters chromatin structure at regulatory sequences to promote terminal differentiation.