The protein arginine methyltransferase Prmt5 is required for myogenesis because it facilitates ATP-dependent chromatin remodeling
The protein arginine methyltransferase Prmt5 is required for myogenesis because it facilitates ATP-dependent chromatin remodeling
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DOI：
10.1128/mcb.01528-06
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发表时间：
2007-01-01
影响因子：
5.3
通讯作者：
Imbalzano, Anthony N.
中科院分区：
文献类型：
--
作者：
Dacwag, Caroline S.;Ohkawa, Yasuyuki;Imbalzano, Anthony N.
骨骼肌分化需要转录因子、组蛋白修饰酶和ATP依赖性染色质重塑酶的协调活性。II型蛋白质精氨酸甲基转移酶Prmt 5对称二甲基化组蛋白H3和H4和许多非染色质蛋白，先前的工作涉及Prmt 5的转录抑制。在这里，我们证明了MyoD诱导的肌肉分化需要Prmt 5。在分化过程中激活的第一个基因之一编码肌生成调节因子肌生成素。Prmt 5和二甲基化H3 R8（组蛋白3精氨酸8）定位于分化细胞中的肌生成素启动子。H3 R8的修饰需要Prmt 5，而Prmt 5的减少导致与SWI/SNF染色质重塑酶相关的Brg 1 ATP酶的启动子结合被废除，以及与基因激活相关的所有后续事件，包括染色质可及性的增加和MyoD的稳定结合。Prmt 5和二甲基化H3 R8也与从肌肉组织分离的活化卫星细胞中的肌细胞生成素启动子相关，进一步证明了这些观察结果的生理相关性。这些数据表明，Prmt 5促进肌生成，因为它是所需的Brg 1依赖性染色质重塑和基因激活在一个基因座分化所必需的。因此，我们得出结论，组蛋白修饰酶是必要的允许ATP依赖性染色质重塑酶的功能。
Skeletal muscle differentiation requires the coordinated activity of transcription factors, histone modifying enzymes, and ATP-dependent chromatin remodeling enzymes. The type II protein arginine methyltransferase Prmt5 symmetrically dimethylates histones H3 and H4 and numerous nonchromatin proteins, and prior work has implicated Prmt5 in transcriptional repression. Here we demonstrate that MyoD-induced muscle differentiation requires Prmt5. One of the first genes activated during differentiation encodes the myogenic regulator myogenin. Prmt5 and dimethylated H3R8 (histone 3 arginine 8) are localized at the myogenin promoter in differentiating cells. Modification of H3R8 required Prmt5, and reduction of Prmt5 resulted in the abrogation of promoter binding by the Brg1 ATPase-associated with the SWI/SNF chromatin remodeling enzymes and all subsequent events associated with gene activation, including increases in chromatin accessibility and stable binding by MyoD. Prmt5 and dimethylated H3R8 were also associated with the myogenin promoter in activated satellite cells isolated from muscle tissue, further demonstrating the physiological relevance of these observations. The data indicate that Prmt5 facilitates myogenesis because it is required for Brg1-dependent chromatin remodeling and gene activation at a locus essential for differentiation. We therefore conclude that a histone modifying enzyme is necessary to permit an ATP-dependent chromatin remodeling enzyme to function.