The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly.
The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly.
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组蛋白甲基转移酶SET7/9促进肌细胞分化和肌原纤维组件。
DOI：
10.1083/jcb.201010090
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发表时间：
2011-08-22
期刊：
影响因子：
--
通讯作者：
Wang DZ
中科院分区：
文献类型：
--
作者：
Tao Y;Neppl RL;Huang ZP;Chen J;Tang RH;Cao R;Zhang Y;Jin SW;Wang DZ
Set7与MyoD转录因子结合，增强肌肉分化所需基因的表达。在骨骼肌分化过程中调节染色质结构的分子事件仍然知之甚少。我们在本文中报道，当成肌细胞分化为肌管时，H3-K4组蛋白甲基转移酶Set7的表达增加，这是骨骼肌发育、肌肉收缩蛋白表达和肌原纤维组装所必需的。Set7基因敲除或显性负性Set7突变体的表达会损害骨骼肌的分化，伴随着组蛋白单甲基化水平的降低(H3-K4me1)。Set7直接与MyoD相互作用，增强肌肉分化基因的表达。在Set7基因敲除的肌细胞中，肌细胞增强因子2和收缩蛋白编码基因的表达减少。此外，我们还证明，Set7还通过阻止SUV39H1介导的H3-K9甲基化来激活肌肉基因的表达。总之，我们的实验确定了Set7在肌肉分化中的生物学功能，并提供了Set7在肌肉分化过程中调节肌源性转录因子的分子机制。
Set7 associates with the MyoD transcription factor to enhance expression of genes required for muscle differentiation. The molecular events that modulate chromatin structure during skeletal muscle differentiation are still poorly understood. We report in this paper that expression of the H3-K4 histone methyltransferase Set7 is increased when myoblasts differentiate into myotubes and is required for skeletal muscle development, expression of muscle contractile proteins, and myofibril assembly. Knockdown of Set7 or expression of a dominant-negative Set7 mutant impairs skeletal muscle differentiation, accompanied by a decrease in levels of histone monomethylation (H3-K4me1). Set7 directly interacts with MyoD to enhance expression of muscle differentiation genes. Expression of myocyte enhancer factor 2 and genes encoding contractile proteins is decreased in Set7 knockdown myocytes. Furthermore, we demonstrate that Set7 also activates muscle gene expression by precluding Suv39h1-mediated H3-K9 methylation on the promoters of myogenic differentiation genes. Together, our experiments define a biological function for Set7 in muscle differentiation and provide a molecular mechanism by which Set7 modulates myogenic transcription factors during muscle differentiation.
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