Distinct Protein Arginine Methyltransferases Promote ATP-Dependent Chromatin Remodeling Function at Different Stages of Skeletal Muscle Differentiation
Distinct Protein Arginine Methyltransferases Promote ATP-Dependent Chromatin Remodeling Function at Different Stages of Skeletal Muscle Differentiation
复制标题
DOI：
10.1128/mcb.00742-08
复制
发表时间：
2009-04-01
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.;Bedford, Mark T.;Imbalzano, Anthony N.
基因表达的时间调控是细胞分化途径的一个标志，但控制不同类型的分化特异性基因表达时间的机制尚不清楚。我们之前证明了II类精氨酸甲基转移酶Prmt5在肌肉形成的早期阶段是骨骼肌分化所必需的（C. S. Dacwag， Y. Ohkawa， S. Pal， S. Sif, and A. N. Imbalzano, Mol. Cell）。生物学报27:384-394,2007)。具体来说，当Prmt5水平降低时，atp依赖的SWI/SNF染色质重塑酶不能与肌生成素（一种重要的早期基因）的启动子相互作用或重塑。在这里，我们研究了Prmt5和I类精氨酸甲基转移酶Carm1/Prmt4在肌肉发生的时间控制中的需求。两种精氨酸甲基转移酶都可以结合和修饰组蛋白的基因晚期调控序列。然而，这两种酶表现出基因表达的顺序要求。早期基因表达需要Prmt5，晚期基因表达不需要Prmt5。晚期基因表达需要Carm1/Prmt4，但早期基因表达不需要。晚期基因需要Carm1/Prmt4的原因是为了促进SWI/SNF染色质重塑酶的相互作用和晚期基因位点的重塑。因此，不同的精氨酸甲基转移酶在骨骼肌分化的不同时期被使用，目的是促进atp依赖性染色质重塑酶的相互作用和肌生成基因的功能。
Temporal regulation of gene expression is a hallmark of cellular differentiation pathways, yet the mechanisms controlling the timing of expression for different classes of differentiation-specific genes are not well understood. We previously demonstrated that the class II arginine methyltransferase Prmt5 was required for skeletal muscle differentiation at the early stages of myogenesis (C. S. Dacwag, Y. Ohkawa, S. Pal, S. Sif, and A. N. Imbalzano, Mol. Cell. Biol. 27: 384-394, 2007). Specifically, when Prmt5 levels were reduced, the ATP-dependent SWI/SNF chromatin-remodeling enzymes could not interact with or remodel the promoter of myogenin, an essential early gene. Here we investigated the requirement for Prmt5 and the class I arginine methyltransferase Carm1/Prmt4 in the temporal control of myogenesis. Both arginine methyltransferases could bind to and modify histones at late-gene regulatory sequences. However, the two enzymes showed sequential requirements for gene expression. Prmt5 was required for early-gene expression but dispensable for late-gene expression. Carm1/Prmt4 was required for late- but not for early-gene expression. The reason for the requirement for Carm1/Prmt4 at late genes was to facilitate SWI/SNF chromatin-remodeling enzyme interaction and remodeling at late-gene loci. Thus, distinct arginine methyltransferases are employed at different times of skeletal muscle differentiation for the purpose of facilitating ATP-dependent chromatin-remodeling enzyme interaction and function at myogenic genes.