首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >skNAC a Smyd1-interacting transcription factor is involved in cardiac development and skeletal muscle growth and regeneration
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skNAC a Smyd1-interacting transcription factor is involved in cardiac development and skeletal muscle growth and regeneration

机译:skNAC是一种与Smyd1相互作用的转录因子参与心脏发育骨骼肌生长和再生

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摘要

Cardiac and skeletal muscle development and maintenance require complex interactions between DNA-binding proteins and chromatin remodeling factors. We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac regulatory proteins. Here we show that the muscle-specific transcription factor skNAC is the major binding partner for Smyd1 in the developing heart. Targeted deletion of skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation that were similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle-specific transcription factor down-regulated in hearts lacking Smyd1, also depended on the presence of skNAC. Viable skNAC−/− adult mice had reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells isolated from skNAC−/− mice had impaired survival compared with wild-type littermate satellite cells. Our results indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration in mice.
机译:心脏和骨骼肌的发育和维持需要DNA结合蛋白与染色质重塑因子之间复杂的相互作用。我们先前曾报道Smyd1,一种肌肉受限的组蛋白甲基转移酶,对于心脏发生和心脏调节蛋白网络的功能至关重要。在这里,我们显示肌肉特异性转录因子skNAC是Smyd1在发育中心脏的主要结合伴侣。小鼠中skNAC的靶向缺失导致在胚胎第12.5天时部分胚胎致死,心室发育不全和心肌细胞增殖减少,但与Smyd1突变体相似但不那么严重。 Irx4是缺乏Smyd1的心脏中下调的心室特异性转录因子,其表达也取决于skNAC的存在。可行的skNAC -/-成年小鼠心脏毒素诱发的损伤后,其出生后骨骼肌生长降低,再生能力受损。与野生型同窝幼仔卫星细胞相比,从skNAC -/-小鼠中分离出的卫星细胞存活期受到损害。我们的结果表明,skNAC在小鼠心室心肌细胞的扩张中起着至关重要的作用,并调节小鼠出生后骨骼肌的生长和再生。

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