Ohkawa Yasuyuki, Marfella Concetta G A, Imbalzano Anthony N
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
EMBO J. 2006 Feb 8;25(3):490-501. doi: 10.1038/sj.emboj.7600943. Epub 2006 Jan 19.
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.
肌细胞生成素并非肌肉生成起始所必需，而是通过尚不明确的机制参与骨骼肌形成。我们在培养细胞中以及首次在胚胎组织中证明，在基因表达起始之前，决定骨骼肌表型的成肌晚期基因会被MyoD结合。在肌肉特化开始时，晚期基因位点处发生了从MyoD到肌细胞生成素的转变，同时伴随着HDAC2的丧失、Mef2D调节因子和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，在没有MyoD的情况下，肌细胞生成素和Mef2D的异位表达足以以完全依赖Brg1的方式诱导肌肉分化。这些结果表明，肌细胞生成素通过与Mef2D合作招募一种ATP依赖的染色质重塑酶来改变调控序列处的染色质结构，从而促进终末分化，进而决定肌肉表型。
