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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The myocardin-related transcription factor, MASTR, cooperates with MyoD to activate skeletal muscle gene expression
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The myocardin-related transcription factor, MASTR, cooperates with MyoD to activate skeletal muscle gene expression

机译:心肌相关转录因子MASTR与MyoD协同激活骨骼肌基因表达

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摘要

The myocardin family proteins (myocardin, MRTF-A, and MRTF-B) are serum response factor (SRF) cofactors and potent transcription activators. Gene-ablation studies have indicated important developmental functions for myocardin family proteins primarily in regulation of cardiac and smooth muscle development. Using Xenopus genome and cDNA databases, we identified a myocardin-related transcription factor expressed specifically in the skeletal muscle lineage. Synteny and sequence alignments indicate that this gene is the frog ortho-logue of mouse MASTR [Creemers EE, Sutherland LB, Oh J, Barbosa AC, Olson EN (2006) Coactivation of MEF2 by the SAP domain proteins myocardin and MASTR. Mol Cell 23:83-96]. Inhibition of MASTR function in the Xenopus embryo by using dominant-negative constructions or morpholino knockdown results in a dramatic reduction in expression of skeletal muscle marker genes. Overexpression of MASTR in whole embryos or embryonic tissue explants induces ectopic expression of muscle marker genes. Furthermore, MASTR cooperates with the myogenic regulatory factors MyoD and Myf5 to activate transcription of skeletal muscle genes. An essential function for MASTR in regulation of myogenic development in the vertebrate embryo has not been previously indicated.
机译:心肌素家族蛋白(心肌素,MRTF-A和MRTF-B)是血清反应因子(SRF)辅助因子和有效的转录激活因子。基因消融研究表明,心肌素家族蛋白的重要发育功能主要在调节心脏和平滑肌的发育中。使用非洲爪蟾基因组和cDNA数据库,我们鉴定了在骨骼肌谱系中特异性表达的心肌相关转录因子。序列和序列比对表明该基因是小鼠MASTR的青蛙直系同源词[Creemers EE,Sutherland LB,Oh J,Barbosa AC,Olson EN(2006)通过SAP域蛋白心肌蛋白和MASTR对MEF2的共激活。 Mol Cell 23:83-96]。通过使用显性负性构建或吗啉代敲除来抑制非洲爪蟾胚胎中的MASTR功能,会导致骨骼肌标记基因的表达急剧减少。在整个胚胎或胚胎组织外植体中MASTR的过表达诱导肌肉标记基因的异位表达。此外,MASTR与肌源性调节因子MyoD和Myf5协同激活骨骼肌基因的转录。先前尚未指出MASTR在调节脊椎动物胚胎中肌发生发展中的基本功能。

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